St Louis Cardinals vs Cincinnati Reds Prediction, Preview and Odds - 05/22/2026

Game Time: 6:40 pm ET, Friday, May 22, 2026

Venue:  Great American Ball Park, Cincinnati, OH 

Where to Watch:  MLB TV

DraftKings:  Moneyline odds:  Cardinals -108, Reds -112; Over/Under:  9.5 runs

Bet365:  Moneyline odds:  Cardinals -110, Reds -110; Over/Under:  9.5 runs

BetMGM:  Moneyline odds:  Cardinals -110, Reds -110; Over/Under:  9.5 runs

St Louis Cardinals:  28-20 (2nd place, NL Central)

Cincinnati Reds:  26-24 (4th place, NL Central)

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St Louis Cardinals:  5-5 last 10

Cincinnati Reds:  5-5 last 10

The Cardinals are entering this series off a loss and lost their 3-game series against the Pittsburgh Pirates 2-1 in their last series. They enter this game with a 28-21 record overall and have a road record of 15-8. This is the series opener of a 3-game series with the Reds on Friday. Their offense ranks 12th in the MLB with a .709 OPS. Dustin May was their starting pitcher on Thursday while Kyle Leahy is making his start in this game on Friday. He is 5-3 with a 3.94 ERA this season. His team won 3 of their last 4 games this season with him making an appearance. In his last MLB regular season appearance, he allowed 1 ER, 0 HR, and 3 BB with 2 SO on 5 hits through 6 IP against the Kansas City Royals.

The Reds are entering this series off a win and won their 3-game series against the Philadelphia Phillies 2-1 in their last series. They enter this game with a 26-24 record overall and have a home record of 13-11. This is the 1st game of a 3-game series with the Cardinals on Friday and they have Thursday off as a day of rest. Their offense ranks 14th in the MLB with a .706 OPS. Andrew Abbott was their starting pitcher on Wednesday while Chris Paddack is making his start in this game on Friday. He is 0-5 with a 7.07 ERA this season. His team lost their last 6 straight games this season with him making an appearance. In his last MLB regular season start, he allowed 2 earned runs, 0 homers, and 1 walks with 3 strikeouts on 6 hits through 5 innings pitched against the Cleveland Guardians.

The current betting odds have the Cardinals listed as a slight underdog in this game according to Draftkings Sportsbook. The Cardinals have looked good in their games this season with their 28-21 record overall which has them right near the top of the NL Central. They have been a great road team too with their 15-8 road record this year. Meanwhile, the Reds have looked good in their games this season with their 26-24 record overall, but that record has them right near the bottom of the NL Central. They have looked good in their own ballpark with their 13-11 home record this season. Neither team has looked great lately as both are 5-5 in their last 10 games, but the Cardinals have looked a lot better on the road this season and they are going to have a big pitching advantage in this one. Leahy is on the mound for the Cardinals here and has looked good this year. He is 5-3 with a 3.94 ERA and the team has been having a lot of success with him. They have won 3 of their last 4 games with him starting and he is off a great start in which he only gave up 1 earned run. The Reds are going with Paddack in this one and he has looked terrible this season. He is 0-5 with a 7.07 ERA this season and he is already on his 2nd team of the year. He wasn't bad in his 1st start with the Reds, giving up 2 earned runs, but that hasn't been a common theme for him this year. He has been giving up a ton of runs in a majority of his starts and he has seen his team lose 6 games in a row now. The Cardinals don't have a bad offense this season either, so they are going to put up runs in this game and will be looking to bounce back from a series loss. Look for the Cardinals to take advantage of this much better pitching matchup. The best way to place a bet here is on the Cardinals to win this game. 

Cardinals Reds Prediction:  Our MLB Pick for Friday, May 22, 2026 (6:40 pm ET start time) is Cardinals 5 Reds 1.

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St Louis Cardinals: 114-102 (+13.2 units) on the moneyline when the money line is +125 to -125. 107-98 (+5.4 units) on the moneyline vs. an NL team with a team batting average of .255 or worse. 85-86 (+11 units) on the moneyline when playing against a team with a winning record. 43-29 UNDER vs. NL teams allowing 4.5 or more runs/game on the season.

Cincinnati Reds: 96-89 (-8.6 units) on the moneyline in home games. 50-63 (-14.3 units) on the moneyline against division opponents. 55-55 (-8.1 units) on the moneyline vs. NL teams allowing 4.5 or more runs/game on the season. 49-27 UNDER when playing against a good team (Win Pct. 54% to 62%).

St Louis Cardinals:  R. Urias (3B) Ten Day IL - Elbow. L. Nootbaar (LF) Sixty Day IL - Heels.

Cincinnati Reds:  J. Trevino (C) Ten Day IL - Hamstring. R. Lowder (SP) Fifteen Day IL - Shoulder. E. Pagan (RP) Fifteen Day IL - Hamstring. B. Williamson (SP) Sixty Day IL - Shoulder. E. Suarez (3B) Ten Day IL - Oblique. C. Ferguson (RP) Fifteen Day IL - Oblique. H. Greene (SP) Sixty Day IL - Elbow.

“We want to make sure that if we go today, and we’re pushing through anything at all that it’s as tolerated, that we’re not going to risk anything further. So, depending on what comes back from that, then we’ll have a plan in place.” - Oliver Marmol on the injury to Masyn Winn.

“I’m just taking everything I learned from last year and putting it into this year. Learning about routines and how to stay healthy during the week. Midweek bullpens and stuff like. Just executing pitches, really.” - Chase Burns on his improvement this season. 

JJ Wetherholt (L) 2B

Iván Herrera (R) DH

Alec Burleson (L) 1B

Jordan Walker (R) RF

Nolan Gorman (L) 3B

Masyn Winn (R) SS

José Fermín (R) LF

Pedro Pagés (R) C

Victor Scott II (L) CF

Matt McLain (R) SS

Elly De La Cruz (S) DH

JJ Bleday (L) LF

Sal Stewart (R) 3B

Spencer Steer (R) 2B

Nathaniel Lowe (L) 1B

Blake Dunn (R) CF

Will Benson (L) RF

P.J. Higgins (R) C

Batting Average:  Jordan Walker (.293)

Hits:  Alec Burleson (53)

Home Runs:  Jordan Walker (13)

RBI:  Jordan Walker (34)

Stolen Bases:  Jordan Walker (7)

Wins:  Kyle Leahy (5)

Saves:  Riley O'Brien (13)

ERA:  Ryan Fernandez (1.59)

Batting Average:  Blake Dunn (.357)

Hits:  Elly De La Cruz (58)

Home Runs:  Sal Stewart (12)

RBI:  Sal Stewart (34)

Stolen Bases:  Sal Stewart (10)

Wins:  Chase Burns (6)

Saves:  Emilio Pagán (6)

ERA:  Chase Burns (1.83)

Managers:

St Louis Cardinals: Oliver Marmol (5th season)

Cincinnati Reds: Terry Francona (2nd season)