This study evaluated the effects of astaxanthin (AX) injected at 1.34 nmol/g body weight on survival, antioxidant capacity, total hemocyte count, and hepatopancreas AX content of the giant freshwater prawn Macrobrachium rosenbergii (De Man 1879) challenged with Lactococcus garvieae. Injected AX significantly increased the survival of M. rosenbergii challenged with L. garvieae (P ≤ 0.05) and enhanced to some extent its antioxidant capacity (superoxide dismutase, glutathione peroxidase, and glutathione reductase) and total hemocyte count. AX-injected M. rosenbergii yielded significantly higher hepatopancreas AX content compared with non-AX-injected control. Overall results of this study indicate that AX plays an important role in enhancing M. rosenbergii resistance against L. garvieae.