The London church was used as a venue for a fashion show by designer Julien McDonald on Monday and featured models both male and female, some with little clothes on.
The aisle of the cathedral was used as the catwalk with hundreds watching on.
Former chaplain to the Queen Rev Dr Gavin Ashenden said the show went against the message of the faith.
Speaking to the Telegraph he said: "The cathedral should ask itself to see if the complaints about the fashion industry - as promoting a narcissistic self-referential display for the very rich - is indeed conducive with the values of the Christian gospel.
"I think the fashion industry is the antithesis of the Christian gospel. It's about the exposure of the poverty of our souls and that's about hiding the state of the soul in an excess of glamour.
"A cathedral ought to think twice before it provides a platform to a cultural venture like this."
Simon Ward is a Christian who ran London Fashion Week for 35 years.
He says the hosting of a show isn't the problem.
"In principle, I think it's a great idea," he said. "It's a question of what's shown in the cathedral and how it's shown.
"If I was the person booking a show into my cathedral I'd have been quite clear in the terms and conditions, there are lines beyond which you will not be allowed to go and if that doesn't work for what you need it for - a cathedral is not the right place for you.
"Personally I think it's inappropriate that people are strutting up and down in a sexualised way because that runs counter to what we believe about humanity, about our relationships, about our bodies."
Southwark Cathedral has defended hosting the show. A spokesperson said: "Southwark Cathedral has over many years been used for a variety of different events, including those related to the fashion industry. We were pleased to be invited to work with the British designer Julien MacDonald as part of this year's London Fashion Week.
"His show brought many people into the Cathedral who might not otherwise have come, and many recognised it as a beautiful and special place.
"The show was delivered in a professional, respectful and energetic way."
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