Newcastle captain Jamaal Lascelles and Allan Saint-Maximin have both been suffering from the long-term effects of Covid-19.
The club's training ground was closed last month following an outbreak of the virus.
Federico Fernandez and Isaac Hayden have confirmed they both tested positive for COVID-19 during the outbreak, that saw more than 10 individuals at the club test positive.
Now, club sources have confirmed that Lascelles and Saint-Maximin have also been struggling with the virus.
Neither Lascelles nor Saint-Maximin have trained since they contracted the virus, and will only return when they feel well enough to do so and protocols are covered.
Both last played for Newcastle in their 2-0 defeat to Chelsea on November 21.
In his pre-match news conference on Friday ahead of Newcastle's 1-1 draw with Fulham, manager Steve Bruce said it was a "frightening" situation for the players.
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"My thoughts are with the two players, and the welfare of them," he said. "It's frightening when you think they are young and fit and absolutely supreme athletes. If anybody needs reminding of how serious this is, then we have witnessed it.
"We've had vomiting, sores, mouth ulcers, no smell, no taste, but the big thing, and which is the worrying thing, is the welfare of one or two of them. It's not great at all.
"That long-term Covid is something which you wouldn't think possible in young, fit, athletes. Unfortunately, it is so.
"They go for a walk for half an hour and then they want to go back to bed. It's as brutal as that. The fatigue is the one thing that has hit them all. For two of them, it's beyond that. We hope there's light at the end of the tunnel, but some are finding it a struggle."