However, this time, it is not because he has spent most of his career dominating the Blues, rather the fact that he has failed to score against them in eight attempts.
Chelsea are the only club to have ever kept him out for that long, with Russian side Rubin Kazan in second place with an impressive run of four fixtures without conceding to Messi.
He famously missed a penalty against the English giants back in 2012 when Chelsea lifted the trophy and he will be keen to end his barren spell against them.
Messi's been in pretty good knick this season as well, scoring 26 goals and recording 12 assists in 33 competitive games for Barca this season.
And, it turns out the Argentine superstar has been doing something this season to ensure he is tip-top shape for the Chelsea game.
It was Ivan Rakitic who may have sent the Blues a sly warning about their talisman.
RAKITIC REVEALS ALL
When asked about Messi's condition heading into the game, the Croatian midfielder said: “Messi looks very focused, he's been working very hard.
"I don't think I've ever seen him working out so much in the gym - you can really see the results.
"He's been training flat out to be in top shape for some time and we need him."
The all-action midfielder then praised Chelsea's main man Eden Hazard, before stating his worry about Andres Iniesta's long-term future at the club.
On Hazard, he said: “He's probably Chelsea's best player, so we'll need to be fully prepared to try and stop him. He's very quick and will cause us problems in one-on-one moves."
Then, Rakitic made his worrying personal revelation on Iniesta: “I'm worried that Iniesta might leave Barça. I don't even want to think too much about that possibility and nor do the fans.
"He's very important to me and he's a great friend. I just hope stays with us for many more years. He has to follow what his heart tells him to do."
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