"We haven't pinpointed anything, but we can go with [shoulder fatigue]," said Pirates manager Clint Hurdle.
Karstens did not throw on Monday and may not throw on Tuesday before seeing how he feels.
"It's not painful. It's just sore, stiff," said Karstens. "It's taken me longer to feel fresh or normal. I don't want to be stupid about it. I understand there's a month left. Right now, to keep me from preventing anything or making anything worse, the best idea is to skip a start.
"I'm not really sure what's going on. We had it checked out. Everything came back negative. It's something I'm going through right now. We'll do all the stuff to try to prevent it from coming back, and hopefully come back after missing a start."
Karstens has pitched 152 innings in 28 games -- 24 starts -- his most innings since 2006.
"Hopefully, skipping a start will give me extra rest and let my shoulder calm down a bit," said Karstens. "Hopefully, this missed start will make me finish the season strong. That's the disappointing part for me. You want to make all your starts throughout the season."
The Pirates didn't name a replacement for Friday's start against the Cubs in Chicago.