Police said the 68-year-old was involved in an "altercation" with another man in the Montgomerie Arms, East Kilbride.
Officers were called to the pub at 5.45pm on Sunday and the suspect then fled the scene.
The injured man was taken by ambulance to Hairmyres Hospital but died a short time later.
Detective Inspector Mark Henderson, of Police Scotland Major Investigation Team, said: "Our investigation is continuing today and we a following a number of lines of enquiry in relation to this death.
"A post mortem examination will take place later today to establish the exact cause of death, however we are treating the death as murder.
"At this time we are trying to establish the circumstances leading up to this incident and the motive for this murder.