“I pulled a muscle on my downswing trying to hit the ball hard on the second hole,” Mickelson, who started his round on the 10th hole, said in a statement.
“It wouldn’t subside for 10 or 12 seconds. I’m going to go back to San Diego for a couple of days and have a doctor take a look at it but there’s really not much you can do for a pulled muscle.”
The injury scare comes as world number one Tiger Woods battles to regain his health in time for the April 10-13 Masters.
Woods has been plagued by back spasms the past month and did not defend his title at the Arnold Palmer Invitational in Florida last week.
Caddie Jim Mackay indicated that Mickelson withdrew as a precaution.
“He’s trying to get ready for Augusta, hitting a lot of drivers, hitting them a little harder and he hit one… and felt a little pain in his side,” Mackay told NBC television.
“It continued on for a few minutes and he decided he didn’t want to take anything to chance relative to what’s going on the next couple of weeks.”
Mickelson, 43, was planning to play the Houston Open next week as a final Masters tune-up, but his participation is now in doubt.
His injury did not seem to be related to a back problem he had earlier in the year, Mickelson said.
“My back’s feeling great, my body’s been feeling great. I felt as good as I have all year. My speed is back, I was hitting the ball hard, driving it great.”
Mickelson barely made the cut at the Texas Open on Friday, after splashing a recovery shot out of the greenside creek at the 36th hole, before sinking a five-foot putt to survive for the weekend.
(Reporting By Andrew Both in Cary, North Carolina, editing by Gene Cherry)