David Sole, 33, of no fixed address, had denied murdering Jonathan Ellison but was found guilty at Lewes Crown Court of beating him to death.
Denise Antonia, 33, of Appledore Road, Brighton, was cleared of murder but found guilty of assisting an offender. She was jailed for five years.
Mr Ellison was found dead in his flat in Gloucester Street on 8 April 2011.
Sole and Antonia were arrested in Winchester, Hampshire, on 16 April following an investigation by Sussex Police's major crime branch.
Following the two-week trial, Sole was told he would serve a minimum term of 18 years.
Det Ch Insp Trevor Bowles said: "Jon Ellison was killed by a man who had befriended him and who he trusted.
"His trust led to his death, as the result of a motiveless but brutal drug and drink-fuelled assault, which caused some of the worst injuries any of us have ever seen."
Mr Bowles said Mr Ellison was a "vulnerable man with many health and personal problems" but he was regarded as "a kind and trusted person".
In a statement issued through Sussex Police, Mr Ellison's brothers said: "He did not deserve to be taken in such a brutal way.
"It was completely at odds with his kind and gentle spirit."
A man has been jailed for life for the "motiveless and brutal" murder of a Brighton man in his city centre flat.