Trichodesmium, a major diazotroph in tropical and subtropical oceans, provides a significant amount of bioavailable nitrogen in oligotrophic oceans. Remarkably, the cyanobacteria carry out nitrogen fixation and photosynthesis simultaneously under high light (HL) conditions. Here, we hypothesize that nickel superoxide dismutase (NiSOD) protects the nitrogen fixation process from oxidative stress generated in photosynthesis under high solar radiation conditions. We found that the variations in nitrogen fixation rates closely corresponded to Ni availability under HL conditions. The expression of NiSOD and two representative photosynthetic proteins also corresponded to variations in both nitrogen fixation rates and Ni availability under HL conditions. Trichodesmium collected in the field had a high Ni quota and elevated SOD activity. The evidence supports the conclusion that NiSOD protects nitrogen fixation in Trichodesmium from oxidative stress. The ability to utilize NiSOD may be a major advantage for Trichodesmium under high solar radiation conditions.