The Swedish striker suffered a hip injury in Saturday's 1-1 draw with Crystal Palace and had to be taken off in the first half, although Eddie Howe confirmed at full time that it was a contact issue rather than a muscle pull.
While the prognosis is positive in that regard, Isak is facing a race against time to prove his fitness for the visit of the league leaders, where Sven Botman (knee), Jamaal Lascelles (knee) and Emil Krafth (shoulder) will all be absent.
Should Isak not be passed fit for the contest, a first Premier League start of the season could await Callum Wilson, who has come off the bench in Newcastle's last two matches after recovering from a back injury.
Wilson did not replace Isak in the first half at Selhurst Park - Harvey Barnes was called upon instead - but the 32-year-old should now come into contention for a starting role after coming through his cameos unscathed.
Barnes could also be in line for promotion to the first XI over Joelinton as Howe rotates his resources, but one-time Liverpool youngster Anthony Gordon - heavily linked with a return to the Reds over the summer - ought to reprise his role.
A midfield recall could also await Sean Longstaff, especially if Howe opts to exercise caution over Joe Willock's fitness, as the former rejoins Sandro Tonali and Bruno Guimaraes in the engine room.
However, no changes should be made to the settled backline of Lewis Hall, Dan Burn, Fabian Schar and Tino Livramento, even with Kieran Trippier waiting in the wings.
Newcastle United possible starting lineup:
Pope; Livramento, Schar, Burn, Hall; Longstaff, Tonali, Guimaraes; Gordon, Wilson, Barnes