The two linebackers are among seven inactives the Patriots have declared for the game, a list that also includes safety Steve Gregory and offensive lineman Matt Tennant.
The holes in the Patriots' defense could be a concern headed into a showdown with rookie quarterback Russell Wilson and the Seahawks' offense.
Hightower, who missed the Patriots' last game as well, has been dealing with a hamstring injury. Wide receiver Julian Edelman is also out, the team reported.
The Seahawks inactives include guard John Moffitt and strong safety Winston Guy. The Seahawks' secondary will also be without cornerbacks Jeremy Lane and Danny Gorrer. The Seattle secondary will be tested against the Patriots' offense, led by quarterback Tom Brady and his group of receivers in the late-afternoon showdown.