Priestland suffered a knee injury during the Scarlets' 16-13 Heineken Cup win against Castres in France, while Newport Gwent Dragons forward Lydiate lasted just 16 minutes of his team's Amlin Challenge Cup victory over Italian side Cavalieri Prato at Rodney Parade.
Lydiate limped off nursing an ankle problem, having been plagued by similar troubles earlier this season, notably during the World Cup in New Zealand when he missed part of Wales' pool stage programme.
Wales coach Warren Gatland has already lost World Cup forwards Luke Charteris, Alun-Wyn Jones and Lloyd Burns from his Six Nations plans.
Cardiff Blues centre Jamie Roberts, meanwhile, is continuing to recover from a knee injury that has sidelined him in recent weeks. Wales kick off their Six Nations campaign against Ireland in Dublin on February 5.
Asked about Priestland's injury, Scarlets head coach Nigel Davies said: "We will have to wait and see. Hopefully, it is not too serious."
Priestland is set to be Wales' first choice number 10 in the Six Nations after enjoying an outstanding World Cup and producing several top-class displays for the Scarlets this term.
He was, though, walking around in the changing room following a Scarlets victory that secured them the Pool One runners-up spot and a place among three Heineken teams who now progress into the second-tier Amlin knockout phase.
Lydiate, meanwhile, is also a key part of Gatland's Six Nations strategy, having established himself in an outstanding Wales back-row alongside skipper Sam Warburton and number eight Toby Faletau.
"I am told the injury is to the back of the ankle, but that is as much as I know at this moment in time," Dragons team manager Robert Beale told BBC Wales Sport after the Prato game. "I would rather wait until we get the expert medical advice."
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