Toxicants released during the degradation of cyanobacterial blooms, such as microcystin-LR (MC-LR) and nitrite (NO2-N), affect the growth of aquatic organisms. The freshwater rotifer Brachionus calyciflorus was exposed to solutions with different combined concentrations of MC-LR (0, 10, 50, 100, and 200μgL−1) and NO2-N (0, 2, 4, 6, and 8mgL−1) to assess the combined effects of MC-LR and NO2-N on life cycle parameters and oxidative stress. Single solutions of MC-LR 200μgL−1 and NO2-N 8mgL−1 were toxic to rotifers. MC-LR combined with NO2-N decreased population growth rate (r), survival, and reproduction, but increased reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) contents (p<0.01). Superoxide dismutase (SOD) and catalase (CAT) activities and mRNA expression levels of MnSOD, CuZnSOD, and CAT significantly decreased under high concentrations of MC-LR or NO2-N (p<0.05). ROS levels had negative correlations with antioxidant enzyme activities and expression levels of antioxidant genes (p<0.01). MC-LR and NO2-N had interactive effects on r, reproduction, ROS levels, MDA content, SOD activity, and expression levels of MnSOD and CAT (p<0.05). By contrast, these effects were antagonistic on survival, CAT activity, GSH content, and expression level of CuZnSOD (p>0.05). Results showed that cyanobacterial metabolites act synergistically and antagonistically to cause toxicity to B. calyciflorus. ROS-mediated toxicity was considered the mechanism by which MC-LR and NO2-N induce damage.