Santana has given up 19 earned runs in his last three starts. In the eight starts since he threw a career-high 134 pitches in a no-hitter June 1, Santana has a 6.54 ERA and has allowed 11 homers in 42 2/3 innings.
The Mets believe the injury has caused Santana's surgically repaired shoulder to become fatigued, and he needs to rest and build up arm strength.
"Ever since the ankle injury, basically he's lost his command," Mets manager Terry Collins said. "We don't think he can land properly ... he is using all arm to pitch with, causing some fatigue in his shoulder, (but) no pain. There's just nothing there. So we're gonna disable him and get him some rest. Let the ankle heal and rebuild the arm strength back a little bit."
Santana said his delivery looked different to the team's staff, but he elected to tune it out during games.
"A couple of times, I felt it, but I didn't think about it," he said. "I'm not thinking when I'm pitching on my ankle or anything, I'm just trying to do my job and compete."
Santana reiterated that his surgically repaired shoulder is "fine."
"I'm OK. My ankle is still recovering from that injury, but again I don't think about it," he said. "My shoulder's fine. I don't have any problems. We'll see in the next couple days how it feels, and we'll see what the next steps are."
Mets general manager Sandy Alderson doesn't think Santana will be back until the team completes an 11-game West Coast road trip Aug. 5.
Santana, who missed all of last season after undergoing shoulder surgery, has thrown 110 2/3 innings.
"Johan I think is exhibiting the effects of 100 innings and a sore ankle for the last couple of starts," Alderson said. "We think that the ankle injury may have led to some general fatigue. In light of the surgery and where he's been and what he's accomplished, we've gotten to the point where he needs to get that ankle right and get back to the point where he feels confident about pitching."
Santana tried to talk management and the training staff into letting him stay in the rotation.
"He wanted to pitch," Collins said. "Last night when the game was over and I talked to him, he did admit that he did feel his ankle at certain times. But the one thing he realized was, he threw some pitches last night and it was all arm, and that started to concern me."
Added Santana: "I would continue pitching. But again, like I said from the beginning, it's not just up to me. All along, since the season started, we're in this together. They told me we have to be very careful, and unfortunately it happened to be my ankle, which is OK, but everything else is fine. I'm just gonna recover and go back to competing."
Santana continues to dismiss the notion that his no-hitter June 1 factored into this injury.
"The no-hitter's past, man. You guys are going back to the same thing all the time," Santana said. "But it's past, and it has nothing to do with that."
"I don't think so. I think it has more to do with the ankle than the no-hitter," he said.
Alderson doesn't think there's anything structurally damaged with Santana.
"We think that he will resume a strength and cardio program," Alderson said. "He'll do long-tossing and have the doctors take another look at the shoulder, but we don't think that's an issue."
Santana's next scheduled start was supposed to be Wednesday afternoon against flame-throwing right-hander Stephen Strasburg.
Right-hander Jeremy Hefner, who was promoted from Triple-A Buffalo to replace Santana on the roster, is a candidate to make that start. Highly touted prospect Matt Harvey is another option, but he is scheduled to start Saturday night for Triple-A Buffalo, which makes it unlikely he'd go Wednesday.
"Certainly he would be a possibility," Alderson said of Harvey.
Alderson was noncommittal when asked how Santana's injury would affect the team's approach to the July 31 non-waiver trade deadline.
"This in and of itself doesn't change our approach. I think the results on the field will dictate that," Alderson said. "This will have an impact on us every five days, no question about that."
The Mets (47-46), who have lost seven of their last eight games, entered Saturday night seven games back in the National League East and 5½ games back in the wild card.
Mike Mazzeo is a frequent contributor to ESPNNewYork.com.