"Scott Williams has been released from the 2019 Six Nations squad to continue rehabilitation of his back injury at his region," a statement from Welsh Rugby said on Wednesday.
"It is felt that his injury will preclude him from taking a competitive part in the competition."
Halfpenny has been released back to Scarlets for their PRO14 clash with Benetton on Saturday, along with flyhalf Rhys Patchell and wing Steff Evans.
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Halfpenny has not played since being concussed following a tackle by Samu Kerevi in Wales' 9-6 victory over Australia on Nov. 10.
Lock Seb Davies, loose-forward Josh Turnbull and flyhalf Jarrod Evans have also been released to Cardiff Blues. All six players will report back to Wales training on Monday.
Wales opened their Six Nations campaign with a 24-19 victory over France in Paris and a 26-15 success in Italy.
They next face England in Cardiff in what is a potential title decider on Feb. 23.
(Reporting By Nick Said; Editing by Christian Radnedge and Toby Davis)
