Impacts on marine survival of Atlantic salmon Salmo salar include sea lice Lepeophtheirus salmonis infestation from coastal aquaculture, and ocean climate forcing. These effects may interact because infestation compromises smolt growth and body condition, and thus response to environmental conditions. We hypothesized that migrating smolts exposed to lice from salmon farms would show (i) reduced one sea-winter (1SW) returns to natal rivers and (ii) a shift in relationships between ocean climate and returns. Annual counts of 1SW fish were studied from ten rivers in Ireland, including five “control” systems without salmon aquaculture. Most counts showed a downward trend, consistent with declines in Atlantic salmon populations. Rivers with aquaculture showed lesser returns (mean 33%, range 19–46%) in years following high lice levels on nearby salmon farms. The level of likely lice pressure also modified how annual 1SW returns varied with ocean conditions. Returns to control rivers showed a weak negative relationship with the Atlantic Multi-decadal Oscillation (AMO) in the late summer (September) of the out-migrating year. This negative AMO effect became much stronger for fish migrating in low lice years but was not evident for high lice years. Smolts experiencing mild-to-moderate lice infestation may show greater sensitivity to ocean warming.