Pierre-Paul has a shoulder injury and did not practice all week. Jacobs, who had nine rushes for 75 yards in the 24-21 loss to the Dallas Cowboys on Sunday, will be sidelined with a knee injury.
Pierre-Paul has gone through an injury-plagued season and has recorded 27 tackles, two sacks and one interception this year.
Cornerbacks Corey Webster (ankle) and Trumaine McBride (groin) also won't play against the Redskins.
The Giants (4-7) will most likely need to win out and need some help from other teams to make the NFC playoffs. The team lost their first six games this season and had won four straight before losing to the Cowboys.