Cambridge United supporter Simon Dobbin was set upon as he walked to the railway station following his team’s 0-0 away draw against Southend United on March 21 2015.
He was left unable to walk or talk and died at home in Mildenhall, Suffolk, on October 21 2020, at the age of 48.
Essex Police said medical tests showed there was a direct link between his death and the injuries he had suffered.
Homicide detectives arrested five men, aged 27, 30, 34, 39 and 45, at addresses across south Essex on Friday morning.
Detective Superintendent Stephen Jennings, of the Kent and Essex Serious Crime Directorate, said the investigation showed there was a “direct, causal link” between Simon Dobbin’s injuries from the attack and his death.
He said: “As part of that investigation, this morning we have arrested five people on suspicion of murder.
“We are also speaking to a number of people who we are considering as witnesses in order to gather their accounts.
“Simon’s wife, Nicole, and their daughter, Emily, have been kept updated on our progress every step of the way.
“Simon was a completely innocent party in the disorder that took place that day and his family have been through an unimaginable time.
“The injuries Simon sustained that day did not just change his life, they also changed the lives of Nicole and Emily.
“As a team, we will do everything we possibly can to secure justice for Nicole, Emily and Simon’s wider family and friends.”