Strikers Billy Sharp and Oli McBurnie are ruled out for the rest of the season as they are recovering from respective thigh and foot injuries.
Jack O'Connell, Jack Robinson and Jack Rodwell also remain on the treatment table, while Chris Basham and Sander Berge are stepping up their fitness but are unlikely to feature at White Hart Lane.
Heckingbottom is not expected to make too many changes to the starting lineup that beat Brighton & Hove Albion last weekend, but Chelsea loanee Ethan Ampadu could be one player who is recalled to the side at the expense of Jayden Bogle.
This could see George Baldock move from the back three and into a more natural right wing-back role, with Enda Stevens set to start on the opposite flank.
John Fleck, Oliver Norwood and Ben Osborn are likely to form a partnership in central midfield while Rhian Brewster, who is yet to score for the Blades, could keep his place up front alongside David McGoldrick.
McGoldrick found the net for the seventh time this season against the Seagulls last weekend, which means he has now scored 39% of Sheffield United's Premier League goals this campaign, the highest ratio in the division.
Sheffield United possible starting XI: Ramsdale; Ampadu, Egan, Bryan; Baldock, Fleck, Norwood, Osborn, Stevens; McGoldrick, Brewster
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