The central defender, who has three caps for Argentina, joined Spurs in 2014 but has struggled to establish himself at White Hart Lane.
Jan Vertonghen and Toby Alderweireld have been manager Mauricio Pochettino's preferred pairing this season, backed up by Kevin Wimmer.
And the club announced on their website: "Federico Fazio has joined Spanish side Sevilla on loan for the rest of the season.
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"The defender returns to the team he joined us from in the summer of 2014 having made 32 appearances in our colours to date."
Another player leaving Spurs is Serbia Under-21 midfielder Milos Veljkovic, who has joined Werder Bremen on a permanent deal.
Veljkovic has signed a contract until 2019 and Werder chief executive Thomas Eichin told his club's website: "We have been monitoring Milos for a long time now. This transfer is an investment in the future."
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