Effects of changed levels of dissolved O₂ and CO₂ on marine primary producers are of general concern with respect to ecological effects of ongoing ocean deoxygenation and acidification as well as upwelled seawaters. We investigated the response of the diazotroph Trichodesmium erythraeum IMS 101 after it acclimated to lowered pO₂ (~60 μM O₂) and/or elevated pCO₂ levels (HC, ~32 μM CO₂) for 20 generations. Our results showed that reduced O₂ levels decreased mitochondrial respiration and photorespiration significantly, and increased the net photosynthetic rate by 66% and 89% under the ambient (AC, ~13 μM CO₂) and the elevated pCO₂ level, respectively. Lowered O₂ concentration by 10% increased its N₂ fixation rate by about 9%, and reducing the dissolved O₂ to 60 μM enhanced the N₂ fixation rate by ~139% under AC and only by 44% under HC, respectively. Meanwhile, particulate organic carbon (POC) and nitrogen (PON) production rates increased simultaneously under reduced O₂ levels, regardless of the pCO₂ treatments. Nevertheless, changed levels of O₂ and CO₂ did not bring about significant changes in the specific growth rate of the diazotroph. Such inconsistency was attributed to the daytime positive and nighttime negative effects of both lowered pO₂ and elevated pCO₂. In conclusion, reduced O₂ levels increased N₂ fixation along with increased photosynthetic performance, implying a potentially profound influence of ocean deoxygenation on the N₂ fixer even under the influence of ocean acidification.