The alternative comic, who has recently returned to the live stage after 17 years away, told The Guardian that stand-up has "evolved into a gigantic industry bigger than aerospace or petro-chemicals".
"I've never been to a comedy show at The O2, but I'm told that, apart from those in the first two rows, the comedian is invisible to the audience, who instead focus their attention on giant TV screens," Sayle said.
"I am told that there is often a great atmosphere at a show like this, but it still means that the audience are essentially paying £100 a head to watch telly."
He added: "The comedian could just pack the first two rows with hirelings then simply put on a DVD of their previous tour (again, I'm told the shows don't change much from year to year) and pay a Romanian Big Issue seller to caper about on stage."
Sayle continued: "It seems that if you want to cater to the comedy mass market, you have to keep your material extremely bland, telling people stuff they already know about such safe subjects as child-rearing and sheds."
The stand-up did however praise the "a mini-revival of that old Soho spirit" led by Stewart Lee's upcoming Comedy Central show The Alternative Comedy Experience, which will feature Robin Ince, Isy Suttie, Josie Long, Tony Law, Bridget Christie and Paul Foot.
Watch an early clip of Alexei Sayle on the first episode of O.T.T. below: