Messi was forced off in the 17th minute after falling awkwardly on his elbow following a challenge from Franco Vazquez.
The Argentina international had already doubled Barca's lead after an early strike from Philippe Coutinho but Ernesto Valverde will be sweating on Messi's availability ahead of fixtures against Inter Milan and Real Madrid in the coming days.
The 31-year-old's evening was brief but he needs little time to make his mark and proved as much with a sumptuous assist for Coutinho inside two minutes. The former Liverpool man curled brilliantly beyond Tomáš Vaclík before Messi's smart finish made it two.
Luis Suarez then won and converted a second-half penalty before a stunning double save from Marc-André ter Stegen kept Barcelona's goal in tact. But the Barca man could not preserve his clean sheet as Pablo Sarabia cut the deficit with a fortuitous deflected strike.
The pick of the goals came at the death as Ivan Rakitic fired a superb volley into the far corner, but there was still time for Luis Muriel to hand Sevilla a deserved second.
The victory sends Barca top of La Liga with Real Madrid four points back in fifth after their defeat to Levante earlier on Saturday.