The five-time Ballon d'Or winner is still scoring at an incredible pace of one goal per game on average across all competitions this season, and Real Betis will be the next team in his sights on Sunday.
The La Liga leaders could take another step towards defending their crown with victory at the Estadio Benito Villamarin, although they face a Betis side with lingering aspirations of breaking into the European places.
Betis recorded a famous 4-3 win at Camp Nou in the reverse fixture earlier this season, but to get anything out of Sunday's match they will likely need to subdue the maestro that is Messi.
Here, Sports Mole looks at how the Argentine has fared against this weekend's opponents in the past.
Just as he has done this season, Messi has averaged a goal per game in his 20 previous meetings with Betis across all competitions, in addition to eight assists.
Sixteen of those goals - and all eight assists - have come in league fixtures between the two sides, and November's meeting was the first time that Messi had ever ended up on the losing side in a top-flight encounter.
The Argentine actually only scored once in his first five games against Betis, and has failed to score in half of the 18 La Liga games, but when he does net he more often than not bags a brace.
Indeed, Messi has scored exactly two goals on seven previous occasions against Saturday's opponents, including in both of the last two games.
However, that brace at the Benito Villamarin last season was only the second game he has scored in at that stadium from seven previous visits, so this weekend's venue is by no means his favourite stomping ground.