Smalling returns to Old Trafford following the end of the Serie A campaign and has not been included in Roma's Europa League squad for the round-of-16 clash with Sevilla.
Sources have told ESPN that Roma wanted a short-term extension to their loan deal to allow him to play in the Europa League, but United refused.
"I'm gutted that I can't finish what we started this season," Smalling wrote on Twitter. "To experience the love shown to me in such a short time was extra special and it will not be forgotten.
"I want to thank and wish all the players and staff the best of luck against Sevilla."
Smalling impressed during his time in the Italian capital and his displays ensured he became a fan-favourite, despite an often difficult campaign for the club.
The 29-year-old made 30 league appearances as Roma finished fifth and contributed three goals.
I'm gutted that I can't finish what we started this season. To experience the love shown to me in such a short time was extra special and it will not be forgotten. I want to thank and wish all the players and staff the best of luck against Sevilla. DAJE ROMA! 💛❤️ 🐺 pic.twitter.com/9vHfpWUNsz— Chris Smalling (@ChrisSmalling) August 4, 2020
Inter Milan had a similar issue with Alexis Sanchez, who spent the season on loan from United and produced some impressive displays towards the end of the season. However, they were able to negotiate an extension to their deal and the Chile international has been included in their squad to face Getafe.
Unlike all other ties in the Europa League, both Roma and Inter will be playing one-off round-of-16 matches with Sevilla and Getafe respectively as the first legs, initially scheduled for March, were postponed due to the coronavirus outbreak.
Information from ESPN correspondent Rob Dawson was used in this report