Police were deployed to Grimesthorpe Road, Burngreave, just after midnight on Friday after a gun was fired towards a group of men stood together in the street.
Three of the men were wounded and taken to hospital but their injuries are not believed to be life threatening.
Two hours later, a 53-year-old man was shot in Club Garden Road, Sharrow.
He was taken to hospital with gunshot wounds to his arm and leg but his injuries are also not believed to be life threatening.
Three weeks ago a 21-year-old man was critically injured when he was shot in Grimesthorpe Road after a gun was fired from one car towards another.
No arrests yet have been made over that incident.
Anyone with information should call South Yorkshire Police on 101.