That meant a change-up in defence, with Moussa Sissoko playing as a wing-back and Toy Alderweireld coming in for Eric Dier - the first time the Englishman has been dropped when available all season.
A refreshed back line did not immediately make for a change in fortunes, however, with the Seagulls opening the scoring.
Leandro Trossard got on the end of Pascal Gross's cross to beat Ben Davies, with Toby Alderweireld powerless on the post.
Even after falling behind, Spurs failed to really get going. Kane's absence wasn't just felt in attack, but in a deeper role where he would ordinarily contribute so much.
In his place, Mourinho had opted for Gareth Bale, Steven Bergwijn and Heung-min Son.
All three looked uninspired and Carlos Vinicius was brought on for centre-back Davinson Sanchez at half-time to inject some life.
There was no one culprit to blame for Spurs' lacklustre attack, but Bale came under particularly heavy fire on social media.
The Welshman didn't have a single shot on target and completed no take-ons.
His former teammate Jamie O'Hara tweeted: "I’ve played with Bale and he always had this inner confidence and self belief, this kind of quiet arrogance," he wrote.
"He seems a shadow of the player I knew."
"Seriously this loan [has] been a disaster," O'Hara added.
Bale was then taken off on 61 minutes, when he was replaced by Lucas Moura.
The forward arrived to so much fanfare in the summer and Spurs fans were elated to see the White Hart Lane icon return from Real Madrid, even acknowledging the injury problems he'd had in the Spanish capital.
Sadly, on current evidence it just hasn't worked out.