Mark McNulty gave the Blades the lead just after the half-hour mark when he turned sharply on the edge of the box before firing home with a fierce effort.
O'Shea almost restored parity just before the break, but he could only drag his shot just wide of the goal.
The visitors levelled the game up six minutes into the second period when Ian Evatt met a cross to powerfully head home.
Chesterfield began to press for the lead and O'Shea forced Howard into a good save on 56 minutes before Gary Roberts curled a free kick over the bar.
The Spireites almost took the lead when Samuel Clucas flashed a shot just wide that O'Shea was close to tapping home.
McNulty saw a header comfortably held by Lee after the hour mark, before Clucas had a goal-bound shot blocked on 74 minutes as the spoils were shared.