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The youngster's club, Arsenal, have given the Royals permission to field Upson in the Worthington Cup, meaning he is 'cup tied' and will not feature for the Gunners in the League Cup this season.
According to Alan Pardew, tonight is a chance for the former Luton Town defender to stake his claim and prove that he deserves a place in the first team.
Pardew told readingfc.co.uk: "Coming here is a good opportunity for Matthew, he needs to show that he's a top class player, and he needs to be a top player to get into our team at the moment."
Upson, meanwhile, was pleased just to get the chance to play ten minutes at Rotherham.
"I was glad to get onto the pitch at Rotherham, it was a difficult time to come into the game as a defender, but it was an interesting game," said Upson, speaking to readingfc.co.uk.
"The manager told me to make sure I got my headers and tackles in, I tried to make some commited challenges.
Looking forward to tonight's game at Cambridge he added: "Cambridge will be a difficult place to go and play, probably similar to the Rotherham game on Saturday.
"I'm looking forward to being a part of the first team squad and geeting more games."
Meanwhile, Graeme Murty will not play tonight, he has not yet recovered from whiplash suffered in a car crash last week.
However, there is good news for Andy Hughes. The midfielder came off with a knock during the Rotherham clash but has recovered in time to take up his place in the starting line up tonight.