Officers were called to The Crane nightclub on Adderley Street in Digbeth just before 11.45pm yesterday (26 December) to reports that the 23-year-old had been stabbed.
Despite efforts to save him, he was pronounced dead around 30 minutes later.
His family has been told and will be support by specialist officers.
Detectives are viewing CCTV from the nightclub and are urging anyone who was in the area at the time to get in touch.
No one has been arrested at this stage.
Det Insp Michelle Thurgood, leading the investigation, said: “This was a young man enjoying himself with friends on a Boxing Day night out and our thoughts are with his friends and family today.
“We know there were hundreds of people in the nightclub at the time. While we’ve spoken to a number of them already, we still need to hear from anyone who was there and who witnessed or even filmed what happened.
“We believe that the victim was approached by a group of people, and was then stabbed, so we’re working hard to identify all of those involved.”
Revellers at the nightclub criticised security searches at the event and described a “moody” atmosphere inside the venue.
Sydnee Power, from Birmingham, described “groups of lads” who were “looking to cause trouble”.
The 23-year-old told the PA news agency: “As soon as me and my friends walked in, we got a very weird vibe and the atmosphere wasn’t good.
“There were just groups of lads everywhere, most of them looked moody.
“A lot of them were definitely looking to cause trouble, they clearly weren’t there to enjoy the music.”
The scene remains closed today while officers gather evidence, and neighbourhood officers will be patrolling the area over the coming days to offer reassurance.
The Crane cancelled its New Year’s Eve event in light of the incident and said it was working closely with police as they continue to investigate.
A statement posted on the club’s Instagram page said: “We are all deeply shocked and saddened that a man lost his life last night as our Boxing Day event came to a close. Our thoughts are with the victim and his family and friends.
“We are working closely with West Midlands Police as they investigate this crime. We encourage anybody who witnessed this incident, or has any information to share which may help West Midlands Police, to contact them directly.
“We do not feel it is right to hold our New Years Eve event under these circumstances. All ticket holders will be contacted directly and refunded by the relevant ticket providers.”