While it is known that Helicobacter species in humans and ferrets can cause gastritis and gastric ulcers, it is unknown if the sea otter bacterium, ‘H. enhydrae’ sp. nov., causes similar gastric diseases. Southern sea otters (Enhydra lutris nereis) are marine mustelids that commonly have gastric ulcers as a significant contributing cause of death. Determining whether Helicobacter infection promotes gastric diseases might aid population recovery by recognizing disease presentation and facilitating treatments. As a first step, we investigated the prevalence of Helicobacter infections in southern sea otters using DNA. Helicobacter DNA was amplified using quantitative polymerase chain reaction from formalin-fixed and fresh-frozen gastric body and pyloric tissues from 46 sea otters using Helicobacter genus 16S rRNA primers. Postmortem examination data and histology were statistically analyzed to uncover associations between Helicobacter presence and gastric diseases. Enrolled sea otters had an 85% Helicobacter spp. prevalence, which is comparable to H. mustelae in ferrets. Fresh frozen tissues showed a higher amount of Helicobacter qPCR-positive samples than did formalin-fixed tissues. Gastric ulcers at the postmortem exam were significantly associated with Helicobacter positivity, while other analyzed factors such as sex, melena, and shark trauma were not correlated. Antibiotic sensitivity analysis show that ‘H. enhydrae’ was sensitive to tetracycline and clarithromycin in vitro. Our data suggest that Helicobacter infections are prevalent in southern sea otters and are associated with gastric ulcers. Our data represents a first step in the study of this potential pathogen, supporting that further work is warranted to assess whether ‘H. enhydrae’ causes or is simply associated with gastric ulcers.