Paxton threw only 17 pitches in two-thirds of an inning, allowing three runs on three hits, including two home runs, before he was removed. Chasen Bradford came into relieve Paxton.
The injury is not believed to be serious, but the Mariners could put Paxton on the disabled list to add a player to the roster for this weekend's interleague series at Colorado.
"Going out in the first inning, you can tell right from the get-go that he was not right,'' manager Scott Servais said after Thursday's 11-2 loss. "He wanted to give it a go and try to battle through it but you could see that it was not the typical James Paxton."
Servais said he expects Paxton to come out of the All-Star break and "be ready to go."
Paxton's start was bumped up a day, taking the place of Felix Hernandez, who was put on the 10-day disabled list for a stiff lower back.
Paxton has 155 strikeouts this season, the fifth-most in the American League and the most by a Mariners pitcher before the All-Star break since Randy Johnson in 1998 (170).
The Associated Press contributed to this report.