Flanker Dan Lydiate has been released from the squad after suffering a serious knee injury in the 21-16 win over Ireland.
Centre Johnny Williams, wing Hallam Amos and scrum-half Tomos Williams will miss the match against Scotland.
Uncapped Halaholo was called up against Barbarians in November 2019.
The 30-year-old centre missed the non-capped international after suffering a serious knee injury playing for his region that ruled him out for almost a year.
New Zealand-born Halaholo qualified through residency after joining the Cardiff Blues in 2016.