The Brazil international was forced off during his side's 3-0 win over Stoke on Sunday after a strong challenge by Charlie Adam.
A statement on Tottenham's official website read: "Following a MRI scan, the club can confirm that Paulinho has sustained significant ligament damage to his right ankle after a heavy challenge from Charlie Adam during Sunday's win against Stoke City.
"The Brazil international was forced off as a result of the injury and is expected to be sidelined for at least four weeks."
The prognosis will see Paulinho sit out this weekend's FA Cup derby with rivals Arsenal, as well as the New Year's Day trip to Manchester United.
He is also likely to miss Premier League fixtures against Crystal Palace, Swansea and Manchester City.
Sky sources claim Spurs are considering complaining to the Football Association about Adam, who is unpopular among the club's fans after two previous tackles on Gareth Bale.
But an FA spokesman has already said no action will be taken over the Paulinho incident after a three-man review panel failed to agree unanimously that the tackle warranted a red card.
Adam, meanwhile, has rubbished suggestions he is guilty of deliberately targeting Spurs players.
"Just for the record and to the people tweeting me abuse saying so, I don't and never have had anything against @SpursOfficial," he tweeted via his account, @Charlie26Adam. "And I would never intend to injure a fellow professional."
Adam first caught Bale during his time at Blackpool in a Premier League game in May 2011. The Welshman was ruled out for three months with ankle ligament damage.
They clashed again during a pre-season friendly between Liverpool and Spurs in the United States in 2012, after which Bale described Adam as a "coward".
Adam was also sent off after collecting a second yellow card for a foul on Scott Parker during Spurs' 4-0 win over Liverpool in September 2011.
The Stoke midfielder's challenge on Paulinho also led Spurs and Brazil team-mate Sandro to wade into the debate, if only in tongue-and-cheek style.
The 24-year-old posted "Charlie Adams - THE BEAST IS WATCHING YOU!!!" via his Twitter account, with a link to a photo of him staring ominously into a camera.