Kieran Trippier, Mauricio Pochettino's new first-choice option at right-back following Kyle Walker's move to Manchester City, limped off during a pre-season victory over Juventus with an ankle problem.
After undergoing a scan, Tottenham have now confirmed the 26-year-old has suffered minor ligament damage that rules him out of the trip to St James' Park, although the north London side are expecting a "short recovery time."
Georges-Kévin Nkoudou will be another absentee on Sunday having failed to recover from a foot injury. The former Lyon starlet impressed during the club's pre-season campaign before the knock also ruled him out of the final match against Juventus.
Trippier and Nkoudou remain on the sidelines along with long-term absentees Danny Rose and Erik Lamela. Rose has not played for the club since the end of January when he suffered a knee ligament injury in a goalless draw against Sunderland that required him to see a specialist and undergo surgery during the summer.
The England international is not expected to return until October but also threw his future at the club in doubt in a tell-all interview released on Thursday where he questioned the club's ambition transfer policy. Rose has since apologised to his Tottenham teammates for his "ill-judged" comments.
Lamela meanwhile has not featured since October 2016 due to a mysterious hip problem. The Argentina international also went under the knife to address the problem over the summer and is expected to miss the opening weeks of the new season.