The game will be played against a backdrop dominated by Pep Guardiola's decision to step down from his coaching position at Barcelona at the end of the season to "recharge his batteries" after four trophy-laden years at the Nou Camp.
The announcement came at the end of a bad week for the club, with Real Madrid having all but sealed the league crown with a 2-1 win in Catalonia last Saturday and Chelsea knocking the holders out of the Champions League by securing a 3-2 aggregate victory in the semi-final second leg on Tuesday.
Rayo, meanwhile, head into Sunday's game on the back of three straight losses in La Liga but knowing they can guarantee their survival this weekend - they sit nine points above the drop zone after 34 matches.
Midfielder Michu said at a press conference: "It is a mystery as to what mood [the Barcelona players] will come here in, but the players they have are of the highest level.
"They are the best in the world in their positions and it will be a tough game for us."
He added: "We really want to regain our consistency. Recent results have not favoured us but our game has been good. We look forward to ensuring our safety mathematically."
Rayo coach Jose Ramon Sandoval could be forced into as many as five changes from the side that lost 2-1 to Sporting Gijon last weekend for the visit of Barca.
Mikel Labaka and Jose Casado are suspended, while Emiliano Armenteros has been ruled out with a calf problem and Raul Bravo and Rober are also doubts due to knocks they picked up in the Sporting game.
Alejandro Arribas and Tito both return from suspension, though, and should take their places in defence, while Jorge Pulido is in line for a recall at centre-back and Michel could also make his long-awaited return in midfield to allow Roberto Trashorras to deputise for Armenteros in a more attacking role.
For Barcelona, Gerard Pique was kept in hospital overnight after the Chelsea game as he suffered a head injury when clashing with his own goalkeeper Victor Valdes and the Spain defender is expected to miss the trip to Rayo.
Midfielder Xavi is also out for two weeks as he continues to feel the effects of a calf injury that has bothered him for the past few months.
Last Saturday's loss against Madrid left Barca seven points behind Jose Mourinho's leaders with four games left.