In Zebo's absence, coach Joe Schmidt named four uncapped backs including New Zealand-born, Samoan-qualified centre Bundee Aki who became eligible for selection for the first time having spent the last three years at Connacht.
Zebo, who has played 35 times for Ireland at wing and fullback and is Munster's record try scorer by some distance, will leave at the end of the season after the province was unable to match offers from several European clubs.
While Ireland continued to pick Zebo's British and Irish Lions team mate Johnny Sexton during a two-year stint in France, other players who moved abroad and ended their contracts with the national union have not been considered for selection.
The would probably mean Zebo, 27, will not be part of Ireland's plans for the 2019 World Cup in Japan.
Fellow 27-year-old Aki was outstanding when Connacht won the Pro 12 championship in 2016 and was named player of the season. With Garry Ringrose and Jared Payne out through injury, he will likely battle it out with in form Ulster centre Stuart McCloskey for a place in the midfield with Robbie Henshaw.
Leinster winger Adam Byrne and the Munster pair of Chris Farrell and Darren Sweetnam were also included for the first time.
"In what we anticipate will be an incredibly physical Guinness Series plenty will be demanded of the squad," Schmidt said in a statement ahead of the tests with South Africa, Fiji and Argentina.
"We have retained a core of experienced players but have also included a number of promising players that we hope will acquit themselves well."
Ireland squad
Forwards: Rory Best (captain), Jack Conan, Ultan Dillane, Tadhg Furlong, Cian Healy, Iain Henderson, Rob Herring, Dave Kilcoyne, Dan Leavy, Jack McGrath, Sean O'Brien, Tommy O'Donnell, Peter O'Mahony, Andrew Porter, Rhys Ruddock, James Ryan, John Ryan, CJ Stander, Devin Toner, James Tracey, Kieran Treadwell
Backs: Bundee Aki, Adam Byrne, Joey Carbery, Andrew Conway, Keith Earls, Chris Farrell, Robbie Henshaw, Dave Kearney, Rob Kearney, Ian Keatley, Kieran Marmion, Stuart McCloskey, Luke McGrath, Conor Murray, Johnny Sexton, Jacob Stockdale, Darren Sweetnam
(Reporting by Padraic Halpin, editing by Ed Osmond)
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