League Two - Oxford chief rues Holmes departure
The winger scored two goals in seven appearances for the U's but could now be set for a loan move elsewhere.
"Lee did really well for us," chairman Kelvin Thomas told Oxford's official website.
"Unfortunately we have suffered a bit with his success and a lot of clubs have been looking at him, and clubs with deeper pockets than us. Southampton will probably take that opportunity.
"We know one of the clubs he is potentially going to have talked to him about a contract for the next couple of years, so I understand it from Lee's point of view as his contract is up in the summer and we would not be in a position to offer him a contract at that sort of level."