This study investigated the effects of dietary mannooligosaccharides (MOS) from copra meal as a dietary feed additive on growth performance, disease resistance, and immune enhancement of the Pacific white shrimp Litopenaeus vannamei. Experimental shrimp were fed with diets supplemented with 2, 3 and 4 g MOS per kg of pellet feed for 6 weeks prior to evaluation of their growth performance, pathogen resistance to Vibrio harveyi and innate immune responses. No significant differences in shrimp average weight and feed conversion ratios were found among all diet groups (p > 0.05). While phagocytic indices and respiratory burst activities were not significantly different either, bactericidal activities were higher in the MOS-supplemented diet groups than the control group. Furthermore, when all diet groups were challenged with V. harveyi, the groups fed with MOS-supplemented diets showed significantly higher survival rates than the control group on day 3 (p < 0.05). Gene expression analysis showed that transcripts of immune-related genes (anti-lipopolysaccharide factor, penaedin and lysozyme) were significantly induced in the hepatopancreases of MOS-supplemented diet groups in comparison to the non-MOS control group. In shrimp intestines, transcripts of anti-lipopolysaccharide factor, penaedin, lysozyme, crustin and peritrophin showed significant increases in the MOS-supplemented diet groups as well. Therefore, MOS from copra meal were able to modulate immune responses in the Pacific white shrimp, with 3 g/kg of MOS giving the highest bacterial clearance activity and induction ratios of immune-related genes. This work provides evidence for beneficial application of MOS obtained from copra meal towards improving the survival rate and immune system of the Pacific white shrimp.