The Brazilian pulled up with no opposition player near him in the 38th minute at Old Trafford, and was replaced by Daniel Sturridge.
Firmino’s injury was the third of the first half for both sides, with United’s Ander Herrera and Juan Mata already having been forced to leave the pitch inside the opening 30 minutes.
Shortly afterwards, the home side were forced to make their third change of an injury-laden first half, with Jesse Lingard – who had replaced Mata just minutes before – also being pulled off, to be replaced by Alexis Sanchez.
Herrera was the first to drop for United, going off after 27 minutes to be replaced by Andreas Pereira, before Mata joined him in dressing room just five minutes later.
The injury to Lingard, coming only 17 minutes after coming on to replace Mata, capped a bizarre and troubling first half for United boss Ole Gunnar Solskjaer.
The spate of injuries left Solskjaer with nowhere to turn for substitutions in the second half as his team look to dent their rivals’ title hopes and tighten their own grip on the top four.
In a first half dominated by knocks and enforced alterations, neither side was able to take a firm grip of the game, with the visitors dominating possession of the ball without unduly troubling David de Gea in the United goal.
A victory for the Reds will lift them three points clear of Manchester City at the top of the Premier League table, whereas a win for United will help haul them further clear of Chelsea and Arsenal in the race for a top-four finish.