The giant Pacific octopus (Enteroctopus dofleini) is a popular exhibit species in public display aquaria, but information on health and disease is limited. This retrospective review evaluates time in collection and describes antemortem clinical signs and pathology of giant Pacific octopuses in an aquarium setting. Between March 2004 and December 2013, there were 19 mortalities: eight males, 10 females, and one individual whose sex was not recorded. Average time spent in collection for all octopuses was 375 ± 173 days (males 351 ± 148 days, females 410 ± 196 days). Ten (52.6%) of the octopuses were sexually mature at the time of death, six (31.6%) were not sexually mature, and reproductive status could not be determined in three octopuses (15.8%). Minimal changes were noted on gross necropsy but branchitis was histologically evident in 14 octopuses, often in conjunction with amoeboid or flagellate parasites. Senescence, parasitism, and husbandry were all important contributors to mortality and should be considered when caring for captive octopuses.