At 3.20pm on Sunday 11 August police received reports of a serious assault near the Hammer and Pincers pub in Liverpool Road.
Despite efforts, the 49-year-old died at the scene having sustained serious stab wounds.
A 35-year-old man and 39-year-old woman have been arrested on suspicion of assisting an offender and remain in custody.
A police presence remains in the area and enquiries are ongoing.
Chief Inspector Simon Parsonage, who is in charge of policing in Widnes, said:
I would like to reassure those living locally that we are doing everything we can to establish the circumstances of what has happened and extra officers will continue to patrol the area to provide reassurance. If you have any concerns at all please speak to an officer.
Anyone who witnessed the incident or has any information, which could assist the investigation, is urged to call Cheshire police on 101 quoting IML 483194.
Information can also be passed on anonymously, via Crimestoppers, on 0800 555 111.