If Sunday is a chance for "Checo", in a season where Red Bull have won every race bar one, the odds favour dominant teammate Max Verstappen (26) in the rarefied air of Mexico City's Autodromo Hermanos Rodriguez.
"I don't think Max is going to get the warmest reception in Mexico," commented team boss Christian Horner (49) after Verstappen won to boos in Austin last Sunday. "But that's water off a duck's back."
Perez, with 'Never Give Up' prominent on a specially-designed helmet for the occasion, remains positive despite a run of poor form.
"Mexico is my most important weekend of the season and I can’t wait," said Perez.
"We have made some very good steps with the car but didn’t get to fully show our progress due to taking some wrong directions with the set up this past weekend.
"I am optimistic for this week, we know what direction we have to take now so hopefully we get to show that."
Verstappen would not be the triple world champion he is, and winner of 50 grands prix by the age of 26, if he did not want to win every race and that does not change even with the championships done and dusted.
Another victory would put the Dutch driver equal fourth in the all-time lists with France's four-times world champion Alain Prost on 51.
It would also be his 16th of the season, breaking his own record for the most in a single campaign, and equal his 2021 record of most podiums in a season (18).
Perez, a winner twice this year, has been off the podium in his previous four outings and beaten by Verstappen in the last 14.
Verstappen has won four of the last five Mexican Grands Prix while Perez has been third in the last two.
McLaren's Lando Norris (23) also stands on the cusp of equalling a record, albeit unwanted, as the driver with most podium finishes without winning.
The holder is now-retired German Nick Heidfeld, who racked up 13 podiums including eight second places, but Norris is on 12 with six seconds.
Mercedes may fancy their chances more, with seven-times world champion Lewis Hamilton (38) a double winner in Mexico and runner-up in Austin last Sunday before his upgraded car failed a post-race check and was disqualified.
Hamilton was second in Mexico last year and in 2021.
Less familiar names will be seen in Friday's first practice with teams fulfilling obligations to give track time to young drivers.
Australian Jack Doohan (20), son of MotoGP great Mick, will be driving for Alpine while French driver Isack Hadjar (19) has his chance at AlphaTauri and compatriot Theo Pourchaire (20) at Alfa Romeo.
Denmark's Frederik Vesti (21) will take George Russell's (25) Mercedes and Britain's Oliver Bearman (18) replaces Kevin Magnussen (31) at Haas for FP1.
