Skubal left the game in the fourth inning after throwing just 45 pitches and will undergo imaging on Saturday to determine the severity of the injury.
"He said he could keep throwing," said manager A.J. Hinch. "But we weren't even going to have him throw a warm-up pitch. We'll hope for the best, but it was left-side tightness."
Skubal gave up four earned runs on four hits (two home runs) in 3.1 innings of work. Detroit eventually lost the game 8-2, handing Skubal his fifth loss of the season.
The 28-year-old was on track to win his second-straight American League Cy Young award. He left Friday's game with the third-best earned run average (2.26) in all of baseball, second in the AL behind Houston Astros pitcher Hunter Brown.
Skubal is also second in the MLB in strikeouts (224), just four behind Boston Red Sox starter and Cy Young candidate Garrett Crochet.
However, Skubal's 0.86 WHIP still ranks at the top.
Detroit (84-64) currently has a comfortable 7.5 game lead in the American League Central division over the Cleveland Guardians (76-71). After Friday's loss, they have just 14 games left in the regular season.
They'll continue their three-game series against Miami on Saturday with game two set to start at 4:10 p.m. Eastern (22:10 CET).