PSG take on the Red Devils at Old Trafford on Tuesday before the return leg on March 6. Neymar will miss both games with a fractured metatarsal.
Per CNN's Becky Anderson and James Masters, Buffon said:
"I think this is a problem for us. I'm not sure if it's a big problem or a little one. I hope it's only a small problem and that we are nevertheless a team that can thrive without him, it would give us great strength and confidence.
"But I must say that without a player of Ney's caliber, it's going to be heavy going, particularly because in the last two or three months he's in excellent condition both physically and mentally and would have been of enormous help."
Neymar won't be the only one missing, as Edinson Cavani and Thomas Meunier have also been ruled out of the first leg.
United boss Ole Gunnar Solskjaer is not taking anything for granted, though:
PSG can still call upon the likes of Angel Di Maria—who will feel he has a point to prove after his disappointing year at Old Trafford—and Julian Draxler in their stead, but they'll be significantly weakened by the loss of Neymar and Cavani.
Between them, they've scored 42 goals in all competitions this season.
All eyes will fall on Kylian Mbappe in their absence, but he'll evidently miss the pair, with whom he has impressive chemistry:
Buffon, who turned 41 in January, enjoys a good relationship with Mbappe despite their age difference.
When wishing the Italian happy birthday on Instagram, the Frenchman referred to him as "grandpa," which the veteran found endearing: "It's only normal that Kylian, who is 20 and thinks of me as a father figure or even a grandpa, but I think that's nice.
"When I joke about with Kylian we have a friendly rapport, and it feels like we're the same age. The way I see it, we have to find common ground and I have to act in a younger way and he has to think along the lines of someone slightly older perhaps."
Buffon is pursuing a major honour that has eluded him at club level in his illustrious career—the Champions League, in which he has been a runner-up on three occasions—and time is running out for him.
He told the Telegraph's Jason Burt he would love to sign off with the trophy:
"For me the Champions League will forever be the highest level, the best tournament to play in. I say thank you for all the emotion that the Champions League has given me. But I hope to have another opportunity to win it because it would be the perfect end to my career."
This season may not be his last chance, though, as he may remain at the Parc des Princes for the next campaign:
"There is an option for one more year. And I hope to sign the renewal. I think that when in a contract you have the option for a year it's very important that both parties are satisfied. I am satisfied and I hope to stay because I understand the team and myself can grow further in the next year."
Despite his advancing years, he's still able to make a difference for PSG, per ESPN FC's Jonathan Johnson:
Against a resurgent, forward-thinking United side, the Parisians will need him to be at his best over the two legs.
Buffon won't be able to make up for the absences at the other end of the pitch, but he can still have a big say in the outcome of the tie.