The Sweden international striker is the focal point of the summer’s biggest transfer saga after the champions saw a £110million bid rejected by the Magpies.
Isak, who scored 27 goals in all competitions last season, missed the club’s pre-season tour of the Far East with a minor thigh injury, before then training alone at former club Real Sociedad.
Reports this week claimed Isak is “adamant he will never represent Newcastle again” with boss Eddie Howe having already conceded he cannot involve the 25-year-old in his current plans, while such uncertainty exists around his future.
England international Anthony Gordon is likely to deputise at centre-forward.
Newcastle pipped Villa on goal difference to fifth place and qualification for this season’s Champions League but a summer where they have been largely free of profit and sustainability concerns has run far from smoothly.
The Magpies have missed out on a number of top targets, with Liam Delap opting to join Chelsea, Benjamin Sesko choosing Manchester United and Hugo Ekitike moving to Liverpool.
Efforts to sign Yoane Wissa from Brentford have also run into trouble despite DR Congo international, in similar style to Isak, pushing for the move.
Winger Anthony Elanga has joined from Nottingham Forest and should make his debut on Saturday, while defender Malick Thiaw has joined from AC Milan.
It is possible the Magpies might also have Jacob Ramsey available to play against his former club.
The midfielder is on the verge of joining in a £40m deal, which would need to be completed by noon on Friday in order for him to be eligible for the season opener.