United were dismantled by their bitter rivals at Old Trafford with their play at the back coming under heavy criticism.
It means they've now conceded 15 goals in the Premier League this season, five times the amount of current league leaders Chelsea.
That's awkward viewing for Scholes, who last week insisted United have a stronger defence than Chelsea.
Scholes went back and forth with Lewis Gebreselassie from Chelsea Fan TV on an episode of The Overlap recently and the discussion went to Chelsea's backline
Gebreselassie said Thiago Silva, Antonio Rudiger and Andreas Christensen were among the three best central defenders in the world
"Really?" a puzzled Scholes replied. "Well, Liverpool have got the best centre-backs, [Manchester] City have got two great ones, I think United have got two really good ones.
"I think Chelsea are probably the weakest out of the top four defensively."
You have to assume the two 'good ones' referred to are captain Harry Maguire and Raphael Varane, with the former starting alongside Victor Lindelof at Old Trafford;
Manager Ole Gunnar Solskjaer looked furious on the sidelines as his side shipped four in the first half.
Naby Keita opened the scoring inside five minutes before Diogo Jota added a second not long after.
Mohamed Salah added a brace before half-time before completing his hat-trick five minutes after the restart.
Paul Pogba was sent off for a challenge on Keita which saw the Guinea international taken off on a stretcher.
Pressure continues to mount on Solskjaer with United now seventh in the table, three points outside the top four.
Sunday also marked the first time in history that United trailed in a Premier League game by four goals at half-time.
"Today's rock bottom [and we're] low in confidence," Solskjaer said per The Guardian. "Next week is Tottenham away, then it's a Champions League game at Atalanta and the next team who visits us is Manchester City.
"We have to make sure we go into the next training session in the right frame of mind."