The duo were surprise omissions as Juventus announced their 22-man squad for Europe’s premier club competition which begins in the middle of September.
Captain Giorgio Chiellini, who has been ruled out for up to six months with a knee injury, has unsurprisingly been omitted as well.
Mandzukic joined from Atletico Madrid in 2015 and scored as Juventus lost 4-1 to Real Madrid in the 2017 UEFA Champions League final.
Mandzukic’s failure to make the squad could be attributed to the presence of Gonzalo Higuain, who returned to the club this summer after loan spells at AC Milan and Chelsea last season.
Emre Can joined the Italian champions from Liverpool on a free transfer in the summer of 2018, signing a four-year contract and made 37 appearances but he has lost his place in the side this term following the arrivals of Aaron Ramsey and Adrien Rabiot, who have all made the squad.
Speaking while away on international duty with Germany, Can said: "I am shocked and angry. Last week, the club promised me something else.
"Yesterday the coach called me and told me in less than a minute that I was not in the squad.
"I cannot explain it, I have not been given any reason.
"Me and my advisor talked to other clubs [during the summer].
"Had I known before, I wouldn't have stayed.
"Now I draw my conclusions and will talk to the club and my agent."
Juventus have been drawn against Atletico Madrid, Bayer Leverkusen and Locomotiv Moscow for the Champions League group stages.
