Halfpenny, who was named player-of-the-series for the British & Irish Lions during the summer, is one of six changes for Blues for the fixture with the Italians.
Chris Czekaj is called-up on the wing while Lewis Jones will make his first start of the season at scrum half where he is paired with fly half Rhys Patchell, who currently stands joint-top of the point scoring charts in the RaboDirect PRO12.
A new-look pack will see Marc Breeze start at hooker as Matthew Rees is named among the replacements.
Wales international Lou Reed is named in the second row, with Bradley Davies suspended for two weeks following a league disciplinary hearing in Edinburgh.
Andries Pretorius will captain the team from the back row where he is joined by Macauley Cook who comes into the team at blindside flanker. Cory Allen and James Down are also named among the replacements.
Blues won both encounters with Zebre last season, with the Italians claiming a losing bonus point in Parma in November.
However, Director of Rugby Phil Davies admits he has been impressed by Zebre this season and they led table toppers Munster 18-9 at half time in their match last weekend.
“Zebre are a much improved outfit and they have shown in the opening weeks of the season that they are not to be underestimated,” said Davies.
“They have recruited strongly with New Zealand international Brendon Leonard at half back and have the likes of Italian international stalwarts Marco Bortolami and Mauro Bergamasco marshalling the team.
“We were impressed with the way Zebre played against Munster last weekend. They also have a massive pack and they will bring real physicality to the contest.
“The team selected to start is primarily the side that finished the game with Connacht. That is because we want to keep continuity and build on the momentum we had at the end of last week’s game,” he added.
“However, it is also crucial that we give players in the squad opportunities to feature so we can build that depth we need in the squad.”
Cardiff Blues: 15 Leigh Halfpenny, 14 Alex Cuthbert, 13 Owen Williams, 12 Dafydd Hewitt, 11 Chris Czekaj, 10 Rhys Patchell, 9 Lewis Jones
1 Taufa’ao Filise, 2 Marc Breeze, 3 Scott Andrews, 4 Lou Reed, 5 Filo Paulo, 6 Macauley Cook, 7 Josh Navidi, 8 Andries Pretorius (c)
Replacements: 16 Matthew Rees, 17 Sam Hobbs, 18 Benoit Bourrust, 19 James Down, 20 Robin Copeland, 21 Lloyd Williams, 22 Gareth Davies, 23 Cory Allen
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