The two unnamed players trained with the group on Thursday but have both tested positive in the last 24 hours and must now isolate for the next 10 days.
According to PA, the club are confident now other players will have to isolate.
Tottenham experienced huge problems following the September international break with players subsequently ruled out through injury and isolation.
Spurs had won all their league games prior to that break but proceeded to lose their next three following it.
They did however secure a 2-1 win over Aston Villa before signing off for October's international break.
'After the international break there are always huge issues that happen,' manager Nuno Eporito Santo said on Friday.
'We have problems but I will not say before the game.'
For more stories like this, check our sport page .
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