Hypoxia has long been considered to be one of the most drastic abiotic stresses in aquatic environments. However, increasing evidence has shown that hypoxia can also prove beneficial for living organisms. The purpose of our study was to investigate the effects of intermittent hypoxia (IH) exposure on growth performance, intestinal flora, intestinal immunity, and anti-inflammation capacity in juvenile largemouth bass. Growth data showed that IH suppressed the growth of juvenile largemouth bass (the mean final weight of the control fish was 20.5 g, but was 14.76 g in the IH-1 h and 12.88 g in the IH-3 h) by regulating the expression of appetite factors. In addition, IH also reconstructed intestinal flora homeostasis, enriched α diversity, and changed composition. It is worth noting that IH mitigated the cumulative mortality rates (33.3% in C, 13.3% in IH-1 h, 20.0% in IH-3 h) and reversed the development of enteritis after 2,4,6-trinitrobenzene sulfonic acid (TNBS) injection. IH exposure significantly inhibited TNBS-induced mucosal injury and increased goblet cells. These results might be due to enhanced antioxidant (CAT, GSH-PX, T-SOD) and immune capacity (ACP, AKP, LZM). We also found that enteritis increased intestinal endoplasmic reticulum stress (ERS) and proinflammatory response. However, these reactions were significantly less in the IH groups. Taken together, the findings of the current study reveal that the IH exposure suppressed growth but also improved stress resistance via inhibition of ERS and the proinflammatory response in largemouth bass.