In response to concerns that novel infectious agents were introduced through the movement of eggs as Atlantic salmon aquaculture developed in British Columbia (BC), Canada, we estimated the prevalence of infectious agents in archived return‐migrating Sockeye salmon, from before and during aquaculture expansion in BC (1985–94). Of 45 infectious agents assessed through molecular assays in 652 samples, 23 (7 bacterial, 2 viral and 14 parasitic) were detected in liver tissue from six regions in BC. Prevalence ranged from 0.005 to 0.83 and varied significantly by region and year. Agent diversity ranged from 0 to 12 per fish (median 4), with the lowest diversity observed in fish from the Trans‐Boundary and Central Coast regions. Agents known to be endemic in Sockeye salmon in BC, including Flavobacterium psychrophilum, Infectious haematopoietic necrosis virus, Ceratonova shasta and Parvicapsula minibicornis, were commonly observed. Others, such as Kudoa thyrsites and Piscirikettsia salmonis, were also detected. Surprisingly, infectious agents described only recently in BC salmon, Ca. Branchiomonas cysticola, Parvicapsula pseudobranchicola and Paranucleospora theridion, were also detected, indicating their potential presence prior to the expansion of the aquaculture industry. In general, our data suggest that agent distributions may not have substantially changed because of the salmon aquaculture industry.