Nuno Espirito Santo's side head into the contest at Bramall Lane with this Premier League fixture viewed as their most important of the season.
With three matches remaining, Forest sit just one point above 18th-placed Luton Town, who will move the East Midlands outfit into the relegation zone if they can defeat Everton on Friday night.
However, a resurgent Burnley, who Forest play on the final day of the season, are now just two points before Nuno's side, despite remaining in 19th spot.
As a result, Forest make the relatively-short trip to Yorkshire looking to end a run of four matches without success and potentially put some breathing space between themselves and the bottom three.
Nottingham Forest keen to end 20-year streak
Although Forest are focused on the game in isolation, they also have the opportunity to end a streak that has lasted since the 2003-04 campaign.
Forest have not managed to complete a league double over the Blades since that season, when the teams were competing in the old Division One.
In the first game at the City Ground, two Marlon Harewood goals helped Forest to a 3-1 triumph, before Marlon King and Gareth Taylor got on the scoresheet in the reverse fixture at Bramall Lane, earning a 2-1 success.
That said, it should be noted that Sheffield United did prevail 3-0 at the City Ground in the FA Cup fourth round during that same season.
This campaign's reverse fixture took place all the way back in the middle of August, Taiwo Awoniyi putting Forest in front before Chris Wood scored an 89th-minute winner after Gustavo Hamer had earlier levelled the score.
History not in Sheffield United's favour
Sheffield United are currently on a run of just one win in nine games against Forest, that success coming at Bramall Lane in April 2019 as they ran out 2-0 victors.
Furthermore, Forest are unbeaten in the last five, but Sheffield United have gone four top-flight home matches against Forest without suffering defeat.
Nevertheless, Chris Wilder's side have gone eight Premier League fixtures without recording a win at their home ground.
They are also just five goals short of equalling the most home goals ever conceded in a top-flight campaign, that total being 56 shipped by Aston Villa in 1935-36.
Wilder is also looking to prevent Sheffield United from conceding at least twice in 10 successive Premier League games. Only three teams have achieved that unwanted streak in the division's history.