Estuarine species frequently encounter areas of simultaneously low dissolved O₂ (hypoxia) and high CO₂ (hypercapnia). Organisms exposed to hypoxia experience a metabolic depression, which serves to decrease ATP utilization and O₂ demand during stress. This down-regulation is typically facilitated by a reduction in protein synthesis, a process that can be responsible for up to 60% of basal metabolism. The added effects of hypercapnia, however, are unclear. Certain decapods also exhibit a metabolic depression in response to bacterial challenges, leading us to hypothesize that protein synthesis may also be reduced during infection. In the present study, we examined the effects of hypoxia (H) and hypercapnic hypoxia (HH), as well as bacterial infection (Vibrio campbellii), on tissue-specific (muscle and hepatopancreas) fractional protein synthesis rates (k_s) in Litopenaeus vannamei. We observed a significant decrease in k_s in muscle after 24h exposure to both H and HH, and in hepatopancreas after 24h exposure to HH. Thus, k_s is responsive to changes in O₂, and the combined effect of hypercapnic hypoxia on k_s is more severe than hypoxia alone. These reductions in k_s appear to be driven by changes in RNA translational efficiency (k_RNA), and not RNA capacity (C_s). Bacterial infection, however, had no significant effect on k_s in either tissue. These results suggest that crustaceans reduce metabolic demand during environmental hypoxia by reducing global protein synthesis, and that this effect is magnified when hypercapnia is concomitantly present. Conversely, an immune-mediated metabolic depression is not associated with a decrease in overall protein production.