Two of the NFL’s top running backs may not be on the field in Week 4.

Saquon Barkley and Austin Ekeler’s injury recoveries have not progressed enough for them to have positive injury designations ahead of their respective games.

That means it could be another tough week for fantasy football players looking to fill their running back depth charts.

De’Von Achane and Jerome Ford emerged as the top waiver-wire pickups over the last two weeks, but if those players are not available in your league, you may have to find some waiver-wire gems to make up for Barkley and Ekeler’s expected production while they continue to heal.

Below is a look at the rest of the significant injuries that will affect Week 4 of the NFL season.

Saquon Barkley Limited In Practice

The good news for the New York Giants is Barkley is practicing ahead of Monday night’s clash with the Seattle Seahawks.

However, the running back is still limited and probably is not at 100 percent after suffering an ankle injury two weeks ago.

The extra day could allow Barkley to test his ankle on Monday morning in an attempt to play. but that could leave fantasy football players in a bind with their rosters.

Matt Breida is the backfield replacement for Barkley, but he struggled to make an impact against the San Francisco 49ers in Week 3.

The last thing fantasy football players want to deal with is picking up an inefficient Breida because they waited until Monday for official news on Barkley.

Of course, you could always operate under the assumption that Barkley will not be close to 100 percent even if he plays. That would lead to a waiver-wire pickup for Sunday’s games.

Chicago Bears rookie Roschon Johnson should be one of the top waiver-wire targets to replace Barkley.

Johnson moved up to the No. 2 spot on the Bears depth chart last week and he is going up against a Denver Broncos defense that has given up the most rushing yards per game of teams that have played three games.

Cam Akers could also be worth a look as well. The new Minnesota Vikings running back takes on the Carolina Panthers and their sixth-worst rushing defense.

Elijah Mitchell and Tyjae Spears are backups who might receive more carries against poor rushing defenses, but they would be options only if no one else is available off the waiver wire.

Austin Ekeler Listed As Doubtful

Ekeler is listed as doubtful, but he will try to make an attempt to play on Sunday, as he told NFL Network’s Bridget Condon.

The Los Angeles Chargers may not be willing to risk Ekeler in Week 4 since they have a Week 5 bye.

The Chargers could give their star running back another week to rest before he returns at full strength.

Joshua Kelley should once again be looked as a fantasy replacement for Ekeler, but he has been underwhelming in the last two weeks with 51 rushing yards.

Los Angeles could rely on its rushing attack more in Week 4 against the Las Vegas Raiders since the Raiders have the 12th-worst rushing defense and more focus could be on Keenan Allen with Mike Williams out due to an ACL injury.

Sunday is probably the last chance Kelley has to break out before he returns to a supporting role in Week 6.

Johnson, Akers, Spears and Mitchell are among the potential waiver-wire replacements for Ekeler if you have not added Kelley already.