Nugent-Hopkins has a labral tear in his left shoulder that likely will need surgery. He was headed to Cleveland on Sunday for an examination.
If surgery is required, the recovery period is expected to be six months, which would cause Nugent-Hopkins to miss the start of training camp in September for the 2013-14 season.
The 20-year-old Nugent-Hopkins has dealt with a shoulder problem since last year, but he had only missed three games this season. During the previous season, he was sidelined for 20 games because of the shoulder.
The Oilers faced the Anaheim Ducks on Sunday night needing a win to stay in playoff contention.
Nugent-Hopkins, the No. 1 pick in the 2011 NHL Draft, had four goals and 20 assists in 40 games this season.
Meanwhile, Calgary Flames forward Curtis Glencross will miss the remainder of the season after suffering a Grade 2 medial collateral ligament sprain, the team announced.
The expected recovery time is four to six weeks, but the Flames have only four games left in the regular season and already are eliminated from playoff contention.
And Florida Panthers defenseman Dmitry Kulikov suffered an upper-body injury in Sunday's loss to Boston and is likely done for the season.
In New York, Islanders forward Kyle Okposo will not face further punishment for the hit he put on Jets defenseman Zach Bogosian, the Winnipeg Free Press reported.