To assess the impact of moderate intermittent hypoxia (dissolved oxygen, DO, 4.0–5.9 mg L−1 O2) on Atlantic salmon growth, food intake, appetite control and innate immunity, a 47-day study mimicking DO conditions observed in sea cages was conducted (hypoxic events occurring on average 3.5 times day−1 and with a mean duration of 69 min). Three treatment groups were studied: normoxia (N), hypoxia fed (HF) and hypoxia feed restricted (HFR). Initial mass and length were measured at the start of the experiment, and sampling was performed at 22 and 47 days. Hypoxia had no effect on the mRNA expression of the appetite regulating factors neuropeptide Y (NPY) and cocaine and amphetamine regulated transcript (CART) measured at day 47. The HF salmon ate 24.8% less between days 22 and 47 as compared with the N group, which was associated with a 23.6% lower overall growth rate by the end of the experiment. Head kidney leucocyte respiratory burst was significantly lower in the hypoxic groups suggesting a negative impact of hypoxia on leucocyte function independent of feeding level. Our results suggest that moderate intermittent hypoxia observed in sea cages in the summer-fall might reduce fish mass gain, and compromise aspects of the innate immune system.