In 28 league appearances against the Rojiblancos, the Barcelona great has scored an astounding 29 times, while his record in all competitions reads 37 goals in 41 outings.
However, the Argentinean has failed to find the net in either of his last two league meetings against the Andalusian outfit.
Messi's goal drought against his favorite foes coincides with the emergence of Jules Kounde as a stalwart in Julen Lopetegui's backline.
The French center-back has faced Messi twice in LaLiga, keeping the 33-year-old quiet on both occasions as Sevilla recorded a win and a draw over the cules while conceding just one goal in the process.
Messi was frustrated again during the teams' recent meeting in the first leg of the Copa del Rey quarter-final, while Kounde oversaw a shutout 2-0 win and broke the deadlock with a stunning solo run and finish.
The pair are set to face off again at the Ramon Sanchez Pizjuan on Saturday in a battle between third and fourth, with just two points separating the sides.
Messi, who tops the standings for the Pichichi trophy with 18 goals so far this season, has never gone three games in a row without scoring against Sevilla.