Everton have conceded the second most goals of any Premier League club this season - 24 - for which their defenders have taken most of the flack.
Keane, for whom Everton could end up paying Burnley £30 million, has had his fair share of the critics, but Barton maintains the 24-year-old is 'top class'.
"Michael Keane is top class - top drawer defender, no doubt about it," said the Liverpudlian, who is a boyhood Everton fan, while co-hosting Monday's Alan Brazil Sports Breakfast on Talksport.
"What’s happened is he’s gone into a back four that’s protecting itself. You’ve got (Leighton) Baines who’s played well in recent weeks but is not at his best. (Phil) Jagielka, (Ashley) Williams - the same. You’ve got the young kid (Jonjoe) Kenny who’s got a lot of improving to do."
Unprompted, Barton then turned on Pickford, another £30 million summer recruit, from Championship strugglers Sunderland.
He added: "I’ll tell you who I think is getting away with murder - the Cat. The Cat’s all over the joint - Pickford. He keeps pushing stuff out. The goal he gives away the other day he palms it straight out. People are forgetting that he got relegated last year [with Sunderland].
"In my opinion there’s a lack of communication, I think (Idrissa) Gueye and (Morgan) Schniederlin in front of them aren’t helping. I think they vacate the middle all the time.
"Everton are in serious trouble."
Despite Everton's struggles this season, both Keane and Pickford, 23, were included in Gareth Southgate's most recent England squad - which was one of the youngest in years.
The pair are in only their third and second full seasons at Premier League level, and a little more patience is perhaps required as they continue to develop.
Does Pickford deserve more of the blame for Everton's struggles this season?