The World Player of the Year has more goals against Atletico than any other domestic rival - 17 in 13 matches, including 14 in La Liga and three in the King's Cup.
His last two games against the Madrid club yielded hat-tricks and the 24-year-old will be looking to add to his 146 league goals in 200 appearances when he takes to the field at the Calderon on Sunday.
Messi netted four against Valencia last weekend, taking his league tally for the season to 27 from 23 matches, one goal fewer than Real Madrid forward Cristiano Ronaldo.
"I have the confidence of my team-mates, the coach and of the people important to me and that makes me happy," Messi said after the Valencia game.
"We just have to carry on enjoying Messi, and he the rest of the team," midfielder Andres Iniesta added.
Despite Messi's exploits, Barca's bid for a fourth straight title has foundered due to their patchy form away from home and they will be 13 points behind Real Madrid if the leaders win at local rivals Rayo Vallecano earlier on Sunday.
Barca have taken 34 of a possible 36 points at the Nou Camp, scoring 50 goals and conceding four. However, on their travels they have won four, drawn five and lost two, with 18 goals for and 13 against.
"We try to prepare all the matches in the same way and it is working very well for us in the Champions League," centre-back Gerard Pique said on Tuesday.
"In La Liga, by contrast, we have found it a bit tougher," the Spain international added.
"I think we are playing well away from home but our opponents are also playing, they are closing ranks very well in defence and it is always difficult to break them down, especially if they take the lead.
"You start to drop points and right now we are in a situation that is not very good."
Real and Barca, the world's richest clubs by income, have again left their poorer domestic rivals trailing and Valencia are 11 points behind Barca in third ahead of their game at home to mid-table Sevilla on Sunday.
Athletic Bilbao occupy Spain's fourth Champions League qualification berth but only two points separate them from 10th-placed Osasuna, with Espanyol, Atletico Madrid, Levante, Rayo Vallecano and Malaga bunched in between.
Osasuna are eight points above the relegation places, which are occupied by Racing Santander in 18th, Sporting Gijon in 19th and Real Zaragoza trailing five points behind Gijon in 20th and last place.
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