Zambrano complained of a stiff back and departed after three innings with the Cubs leading 6-2. Ramirez was hit by a pitch in the left forearm in the 10th inning and left the game dizzy from the pain.
The Cubs won 9-8 in 10 innings. Manager Lou Piniella said Zambrano is expected to make his next start as scheduled, and Ramirez might be able to play Sunday.
Zambrano said he has experienced occasional back trouble throughout his career, but this was the first time this season it became a serious problem.
"I was feeling it the whole game," Zambrano said. "As the game was going and going, it was feeling worse and worse."
The right-hander struggled with his control and said he left the game because he didn't want to risk further injury.
"He was throwing all with his upper body and getting no torque into the ball at all," Piniella said.
Zambrano walked three, threw a wild pitch and hit Hanley Ramirez, forcing the NL batting leader from the game with a bruised left knee. Zambrano said he's unsure what caused his back to flare up.
"It's nothing to worry about," he said. "It's just a tight back. I'll just have to treat it and get ready for my next start."
The three-time NL All-Star was on the disabled list for only the third time in his career May 4-22 with a strained left hamstring.
Amaris Ramirez took his base after being hit by a pitch from Leo Nunez but came out of the game a few minutes later for a pinch runner.
"He's OK," Piniella said. "He was dizzy from pain. We'll see how he feels Sunday."