Barcelona were made to come from behind against 10-man Los Che, who took the lead in the 29th minute through on-loan Manchester City defender Eliaquim Mangala.
Although Munir El Haddadi drew Valencia level nearly immediately against his parent club, the 10 men struggled to contain Messi, who made it 3-2 after 52 minutes but will miss the trip to Granada in the first game back from the global break due to suspension after picking up a late yellow card.
For starters, Andres Iniesta completed his first 90 minutes since the start of January, while Andre Gomes, victim of boo-birds and a former Valencia player, scored his first goal for the club right at the death.
Real top the la liga table with 65 points from 27 games, two ahead of Barcelona's 63 from 28 games while Sevilla are at the third position with 57 points in 28 games, two points ahead of Atletico from same number of games.
Luis Enrique's three-man back line was caught out too often, with Munir denied by keeper Marc-Andre ter Stegen when clean through seconds before Mangala scored from the resulting corner. Neymar then fired over as Barcelona toyed with putting the game beyond doubt.
"The whistling of Andre Gomes is intolerable", said the Spanish global.
The defeat capped a miserable week for Sevilla after they were dumped out of the Champions League by Leicester on Tuesday.
It's a shootout at the Camp Nou today as Barcelona and Valencia are playing a very entertaining match.
Atletico closed to within two points of Sevilla after Antoine Griezmann steered it to a third straight victory. That was his 40th goal of the season.
Also on Sunday Celta Vigo won the Galician derby at Deportivo La Coruna 1-0 thanks to a late goal from Iago Aspas while Sporting Gijon beat Granada 3-1 to leapfrog the Andalusians into 18th but remain in the relegation zone. They were losing at one stage, conceded twice at home and despite scoring three goals they were wasteful at times.