Real Madrid suffered a second successive defeat as Atletico Madrid and Barcelona pulled clear in the Primera Division title race, but Barca's night was marred by a serious injury to goalkeeper Victor Valdes which has likely ended his career with the club and ruled him out of the World Cup.
Sevilla came from behind to beat Madrid 2-1 as leaders Atletico were seeing off Granada 1-0, while earlier in the evening Barca had followed up their 4-3 Clasico victory by beating Celta Vigo 3-0.
However, Barca's celebrations were muted after the news came through on Valdes.
The 32-year-old goalkeeper, who has long planned to leave the Nou Camp at the end of his contract in June, fell awkwardly while saving a free-kick from Fabian Orellana in the 22nd minute of the match, and could be seen crying as he left the pitch on a cart.
Barca confirmed an anterior cruciate ligament tear after the match.
"Victor Valdes suffered an ACL tear on 22 minutes after saving a free-kick," the club said on their website. "The club's medical services confirm that he will need surgery."
The injury leaves an immediate question mark over Valdes' future as it will complicate any move to a new club this summer, while it will come as a blow to Vicente Del Bosque as he finalises his World Cup plans.
Orellana's free-kick appeared to catch Valdes wrong-footed, and although he was able to make the stop he had to dive forward to gather the rebound, and it was then he suffered the injury.
At that point, Barca were already leading 1-0 through Neymar's sixth minute goal, and Lionel Messi doubled the advantage on the half hour before Neymar struck again midway through the second period.
In Seville, Cristiano Ronaldo put Madrid in front with a 15th minute deflected free-kick after he had been fouled by Andujar Coke, but Sevilla replied almost immediately through Carlos Bacca, and in the 72nd minute some superb skill from Ivan Rakitic set up Bacca for the second.
It was a record sixth straight win for Sevilla, lifting them up to fifth, six points behind Athletic Bilbao in fourth.
Atletico lead the way on 73 points after Diego Costa's 63rd minute header was enough to give them all three points at home.
Barca are second on 72 points, with Madrid third on 70.
At the other end of the table, a late penalty from Joaquin Larrivey condemned Osasuna to a fifth straight defeat at the hands of fellow strugglers Rayo Vallecano, who gave themselves a cushion to the relegation zone in a 1-0 win.
A drab match with little quality on display seemed destined to finish goalless until Abella Damia felled Jose Fernandez in the area and Larrivey stepped up to place his spot-kick in the bottom left-hand corner of the net.
The result sees Rayo climb up to 13th in the congested lower reaches of the table, while Osasuna hover just above the drop zone, knowing they will drop into it if either Getafe or Real Valladolid can pick up a result on Thursday.
Barca boss Gerardo Martino bemoaned the news, telling his media conference: "It's a very hard blow. But this team has lived blow to blow for a long time and we will move forward."