This short-term study evaluated the effect of non-lethal high CO 2 concentration on the transcriptional response of immune-related genes of Pacific white shrimp (Litopenaeus vannamei) cultured in recirculating aquaculture systems (RAS). Two experimental groups were created: high CO 2 (47.67±2.04 mg L −1 ) and low CO 2 (2.0±1.93 mg L −1 ). Shrimp of 8.85±1.20 g were placed randomly at a density equivalent to 100 individuals m −3 and were monitored at 6, 12, 18, and 24 h. The transcriptional response of immune-related genes was analyzed by qPCR. Gene expression of hemocyanin, prophenoloxidase, and heat shock protein 60 was downregulated at 24 h, suggesting affectations on oxygen transportation, melanization, and protein functioning of L. vannamei under high CO 2 concentrations. Also, gene up-regulation of lipopolysaccharide-and β-glucan-binding protein and cytosolic manganese superoxide dismutase can impair the bacterial recognition and antioxidant defense of shrimp exposed to high CO 2 concentrations. These results suggest that concentration at about 47 mg L −1 of CO 2 can significantly influence the transcriptional response modulation of immune-related genes.