They had hope when Mathieu Baudry headed them in front with 20 minutes to go but Bob Harris lashed home an equaliser seven minutes later.
O’s boss Fabio Liverani made four changes to the side which lost 1-0 at Rochdale in midweek, with Scott Cuthbert, Lloyd James, Shaun Batt and Jay Simpson coming into the starting line-up.
The O’s were the side on the front foot early doors, though were unable to turn the possession into a goal threat.
And the first real opportunity came to the Blades when Steven Davies paced clear of the defence before squaring for an unmarked Jason Holt, however his effort was straight at an onrushing Cisak who blocked the effort.
Sheffield United were starting to crank the pressure up and Murphy worked an opening just on the edge of the box but Cisak was once more equal to it.
Chances were few and far between on a tense day in E10, but if anyone looked likely to take the lead it was Nigel Clough’s side and Che Adams saw a shot deflected behind for a corner after the hosts only half cleared a ball into the box.
The Blades lost possession inside the O’s half and the hosts launched a counter attack and a move involving Bartley and Cox found its way to Dagnall, however, the striker shot straight at United goalkeeper Mark Howard.
Another Dagnall effort forced a corner and a well-worked move involving Cox and Dagnall saw the ball fall to Batt just inside the area but his effort was tipped over the bar by Howard.
The first half ended goalless, and neither side made any changes for the second period.
Cisak managed to get something on a fierce Adams drive from just inside the box as the O’s failed to clear their line, but again chances were at a premium in the early stages of the half.
But the O’s fashioned a great opportunity down their left hand side with Lloyd James threading a ball through for Simpson who backheeled the ball into the path of an unmarked Cox.
And the winger paced into the box before shooting fiercely at goal, but Howard was able to hold the effort.
That got the O’s fans going and that started a spell of pressure from the hosts. A ball into the box from Dagnall was put behind for a corner as Orient upped the ante.
But like Orient did in the first half, the Blades weathered the storm, however, that was until the O’s took a vital lead with 20 minutes to go.
Dean Cox’s outswinging corner found the head of Baudry and he thundered the header past Howard into the top corner and the O’s hopes of avoiding relegation took a massive boost.
But the lead almost didn’t last long as Holt worked an opening from close range but a fine last-ditch block from skipper Nathan Clarke denied the Blades.
The goal seemed to lift the visitors and Brayford’s goalbound effort was deflected behind for a corner, and from the subsequent set piece Murphy was free at the near post but he blazed over.
However they did find the equaliser in the 77th minute when the ball fell for Bob Harris 25 yards from goal and his effort took several deflections behind finding a way into the back of the net.
And Baxter went close to putting the visitors in front from a 20-yard free-kick which thundered against the post and away from danger.
The O’s went back in search of a second goal and Simpson’s free-kick was tipped over by Howard, but the corner came to nothing and the O's hopes of victory in their final home league game of the season had ended.
ORIENT: Cisak, Cuthbert, Clarke (c), Baudry, Omozusi, Cox, James (Wright 62’), Bartley (Mooney 85’), Batt (McAnuff 52’), Dagnall, Simpson.
SUBS: Lowry, Woods, Hedges, Taylor
BOOKINGS: Batt 22’ Baudry 69’ Cuthbert
GOALS: Baudry 70’
SHEFFIELD UNITED: Howard, Harris, Brayford (c), Basham, Murphy, Baxter, Coutts (Doyle 90'), Freeman, Adams (Calvert-Lewin 66’), Davies (Scougall 66’), Holt.
SUBS: Willis (gk), Alcock, , Davies, Reed.
BOOKINGS: Coutts 68’ Baxter 70’ Calvert-Lewin 82’, Harris 86’
GOALS: Harris 77’
ATTENDANCE: 7249 (1338 Sheffield United fans)