The latest addition to the list is Destiny Udogie who has been ruled out for six weeks with a hamstring injury he picked up in the 2-2 draw at home to Wolves on Sunday.
The Italian left-back had a torrid time with injuries last season, having surgery on a quad injury which ruled him out for the season and the Euros during the summer.
During the clash with Wolves, Udogie came off in the 50th minute as it added another defensive absentee to Postecoglou's growing list.
Udogie joins Cristian Romero, Micky van de Ven and Ben Davies in the treatment room - leaving Radu Dragusin as the only fit senior centre-back - and even the Romanian was forced to play through injury against Wolves.
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Speaking of team selection woes on Friday, Postecoglou said: "Destiny is his hamstring. Looks around six weeks for him.
"We lose [Rodrigo] Bentancur suspended. None of the injured ones are back yet. We've had a bit of an illness bug with a few not training.
"At this stage Richarlison and Mikey Moore are the next cabs off the rank, we're hoping next week. Davies, Van de Ven and Romero all kind of around the same time, back end of January."
When asked about the possibility of losing more players to the sickness bug, Postecoglou added: "Not sure yet."
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How Tottenham could line-up against Newcastle
Tottenham have a busy schedule to kick off 2025, including a north London Derby at the Emirates and the Carabao Cup semi-final against Liverpool.
Djed Spence will return from suspension after picking up a red card against Nottingham Forest and it is expected that he will step in for Udogie at left-back for Newcastle's visit.
Pedro Porro, Radu Dragusin and Archie Gray will likely feature along the backline with Spence.
Yves Bissouma and Pape Sarr are likely to start in midfield alongside Dejan Kulusevski.
Postecoglou's favoured front three looks poised to include Heung-min Son and Dominic Solanke, while Brennan Johnson will hope to start over James Maddison after scoring against Wolves.
Brazilian forward Richarlison has also been out with a hamstring injury since November.
Winger Wilson Odobert who joined from Burnley in the summer is also sidelined.
Goalkeeper Guglielmo Vicario broke a bone in his ankle during the 2-1 victory over Man City in the Carabao Cup, despite playing for 60 minutes with the injury.
Fraser Forster has stepped in as the side's new number one whilst the Italian keeper is out, although Tottenham's recent torrid form has prompted the club to look for replacements in January.
Tottenham boss Postecoglou is said to be eyeing a move for Wolves goalkeeper Sam Johnstone.
Spurs are also considering a January swoop for defender Fikayo Tomori, talkSPORT understands.
Newcastle, West Ham and Brentford are also keen on the former Chelsea centre-back amid his recent struggles at AC Milan.