The 34-year-old missed Wednesday's 2-1 victory away at Metz due to bone bruising on his knee and he is also a major doubt for their Champions League encounter with Manchester City next week.
Messi's Argentine compatriot Mauro Icardi is set to remain in the starting lineup as a result, with both Neymar and Kylian Mbappe expected to join him in a powerful three-man attack.
Mauricio Pochettino has at least four other players ruled out for this weekend's fixtures, as Sergio Ramos (calf), Marco Verratti (knee), Juan Bernat (ACL) and Ismael Gharbi (thigh) continue to recover from their respective injuries.
Meanwhile, PSG full-backs Layvin Kurzawa (calf) and Colin Dagba (ankle) are doubtful and will be assessed ahead of kickoff to see if they can feature in the matchday squad.
Pochettino is expected to tinker with his starting lineup in a few positions due to their busy fixture schedule.
Abdou Diallo will be hoping to return to the first XI at the expense of Nuno Mendes, while Ander Herrera could be handed a start in midfield, which would likely see Rafinha drop to the bench.
Achraf Hakimi - who scored a brace in midweek - as well as Marquinhos and Presnel Kimpembe are expected to remain in defence, while Keylor Navas could once again keep the number one jersey ahead of summer signing Gianluigi Donnarumma.
PSG possible starting lineup: Navas; Hakimi, Marquinhos, Kimpembe, Diallo; Danilo, Herrera, Wijnaldum; Neymar, Icardi, Mbappe
Fiorentina 
Udinese 
Benfica 
Estoril 
Inter 
Como 
Manchester City 
Everton 
Chelsea 
Fulham 
Nottingham Forest 
Tottenham 
Celtic 
Motherwell 
Wolverhampton 
Manchester Utd 
ST Mirren 
Rangers 
Sampdoria 
Carrarese 
Liverpool 
Leicester 
Arsenal 
Ipswich 
Cagliari 
Lazio 
Atalanta 
FC Porto 
Boavista 
Torino 
Napoli 
Venezia 
ST Johnstone 
Juventus 
West Ham 
Pisa 
AC Milan 
Roma 
Sporting CP 
Newcastle 
Brentford