The 24-year-old Scot had been coasting along at 6-2, 2-1 and deuce on German Michael Berrer's serve when he jarred his right ankle badly trying to run down a drop shot.
Murray won the point, but he hopped about in agony and then collapsed onto his back in the red dirt of the Suzanne Lenglen showcourt.
After taking painkillers and having the ankle strapped at a medical time-out, Murray resumed to clinch the break and lead 3-1.
But clearly still in some discomfort, he then dropped serve for the first time in the match and screamed out his frustrations at his coaching staff in the tribunes.
Limping between rallies and looking distraught, Murray somehow dug in to break the Berrer serve again and then held his own comfortably enough to lead 5-2.
Murray took the set 6-3 to go two sets up, but he still looked in some discomfort and requested another medical time-out from the umpire at the next change of ends.
Another break in his favour gave him the perfect start to the third set and he then won the next three games to go 4-0 up.
Murray duly wrapped up a third straight straight sets win but there will be serious doubts about his fitness ahead of his fourth tie against Serbian Davis Cup hero Viktor Troicki on Monday.
The 15th seeded Troicki saw off Alexandr Dolgopolov of Ukraine 6-4, 3-6, 6-3, 6-4 to reach the last 16 of a major event for the first time.
Nadal made it through to the fourth round with a 6-1, 6-3, 6-0 win over Croatian qualifier Antonio Veic in a centre-court mismatch.
It was the Spaniard's 41st win at Roland Garros against just the one defeat since he made his debut in 2005, but such was the paucity of the opposition that the win will answer few questions about his actual form.
His next opponent will be either compatriot Fernando Verdasco, against whom he has a 11-0 win-loss record, or Croatian veteran Ivan Ljubicic, who were in action on Court 1 later Saturday.
Nadal had admitted he was struggling to find his best form after two uncustomary tough opening rounds against giant American John Isner, who took him to five sets, and Spanish compatriot Pablo Andujar.
But he wasted no time in getting on top of Veic, the world number 227, who made it through the qualifiers and then scored a five sets win over Russia's Nikolay Davydenko to reach the third round in what was just his second major event.
The five-times defending champion smoothly moved 4-0 ahead before Veic got off the mark but the first set was pocketed by the Spaniard 6-2 in just 26 minutes.
Veic put up some resistance at the start of the second and had a break point but Nadal erased that with a big crosscourt forehand after a bruising rally.
That was about as good as it got for the Croatian who found himself overpowered by the five-times champion for the remainder of a one-sided contest.
- AFPTags: sport, tennis, france