It happened just after 4am on Saturday morning at The Establishment in Victoria Square.
The men, who are both 21 and from the Widnes area, were both arrested on suspicion of section 20 assault.
One of the men has since been released under investigation pending further investigation; the second man remains in police custody where he is assisting officers with their enquiries.
The victim remains in Walton Hospital where his condition is described as critical but stable.
At around 4.05am on Saturday a 22-year-old local man was assaulted on a dancefloor at The Establishment nightclub in Victoria Square.
Cheshire Constabulary is urging anyone who recognises them or thinks they may know their identities to come forward.
Detectives also want to speak to anyone who witnessed the incident or has any other information that may aid the investigation.
Anyone with information that may aid detectives with their investigation, no matter how small, should call Cheshire Constabulary on 101, quoting IML 275713.
Alternatively information can be given anonymously by contacting Crimestoppers on 0800 555 111.