Player/coach Dan Coultas revealed that the squad will be missing several key players as the game is at 11.30am (Fettes College).
Grange beat Watsonians 4-2 in the men's Premiership last weekend and Coultas, a former Great Britain squad player, thought they were tough opponents.
He added: "We will take that into this weekend and will try to improve in a few key areas. We know it will be another tough game but if we can be clinical when we get chances then it could be a close one."
Watsonians also have their final league game before the winter shut-down on Sunday and he said: "We would also like to do well here, but are again facing players being unavailable for various reasons.
"We will still be going to Uddingston to fight for three points and finish as high up the table as possible at the break."
The cup fixture is the feature tie of the round with Grange, second in the top division, against a side in fifth spot.
The round also features another all Premiership clash with third-placed Edinburgh University hosting sixth-placed Clydesdale (11.30am, Peffermill).
Inverleith, boosted last weekend’s 7-1 Premiership victory over Kelburne, host Strathclyde University (Mary Erskine School, 13.30) who are third in the National League.
Coach Chris Duncan has James Stuart back after injury and he saidd: "We have to be on our toes to avoid any chances of a slip-up.”
Free-scoring Erskine Stewart’s Melville, who top the National League, entertain former Premiership pace-setters Dunfermline Carnegie (Inverleith Playing Fields, no time given)