Objective We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)‐2 vaccinations and assessed the utility of CAV‐1 and CAV‐2 titers in elucidation of its etiopathogenesis. Animals studied Nine dogs with unexplained keratouveitis (14 eyes) and nine control dogs. Procedures The Animal Health Trust clinical database was searched between 2008 and 2018 to identify cases of keratouveitis. Inclusion criteria included known vaccination status, interval from vaccination to development of clinical signs and availability of CAV titers. Cases were excluded if they were older than 1 year of age, or other causative ocular pathology for corneal edema was identified. Nine age‐matched dogs without corneal edema but with CAV titers were included as controls. Results Mean CAV‐1 and CAV‐2 titers were not statistically different between dogs with keratouveitis and controls (p = .16 and p = .76, respectively). Three cases had CAV‐1 titers >5000 and two of these cases had rising convalescence titers (greater than an 11‐fold increase) suggesting infection with wild‐type CAV‐1. The six other cases did not appear to be associated with CAV infection or vaccination. Conclusion Keratouveitis continues to occur despite the advent of CAV‐2 vaccinations. While this study found no evidence to indicate CAV‐2 vaccination causes keratouveitis, the data indicates that in a proportion of cases, contemporaneous wild‐type CAV‐1 infection is a possible cause.