An air of uncertainty has surrounded Barcelona recently with reports of backroom unrest compounding rumours that star player Lionel Messi wants to leave the Catalan club.
A loss to Real Sociedad in their last league outing has not helped matters, and Atletico will be full of confidence after seeing off city rivals Real Madrid 2-0 in the Copa del Rey on Wednesday.
The two sides have played out five draws in their last six meetings, with Atletico's 1-0 win in the Champions League quarter-finals last term the only victory either side have enjoyed over the other in the last two seasons.
The clash could also see Fernando Torres make his first league appearance for Atletico since he left the club in 2007, with the 30-year-old playing 60 minutes in his side's cup fixture midweek.
Real Madrid will be hoping to arrest their current form slump when they take on Espanyol at The Santiago Bernabeu on Saturday.
Carlo Ancelotti's side saw their 22-game unbeaten run snapped by Valencia in their last league outing before their loss to Atletico, but they will be confident against an Espanyol side who have also lost their last two games and have not tasted success against Real since 2007.
Also on Saturday, Malaga will be hoping to jump back into the European places when they are visited by sixth placed Villarreal, a side who have not lost a league game since early November.
Valencia will be confident of claiming all three points when they travel to Celta Vigo while surprise packets Eibar take on a Getafe outfit that have not tasted success in their last seven league outings.
Levante were last victorious in the league when they beat Valencia 2-1 in November, but will have a good chance to reverse their slide down the table when they host fellow strugglers Deportivo La Coruna on Friday.
Fifth-placed Sevilla travel to Almeria in Sunday's early kick-off as they attempt to shore up their grip on a Europa League spot.
Cellar-dwellers Elche face a tough trip to Athletic Bilbao on Sunday, while Granada will be looking to end a five-game winless streak in all competitions when they host Real Sociedad, who followed up their victory over Barcelona with a Copa del Rey loss to Villarreal.
Lowly Cordoba close out the round when they travel to Rayo Vallecano on Monday, with a win likely to see them climb out of the relegation zone.