Little is known about the combined impacts of future CO2 and temperature increases on the growth and physiology of marine picocyanobacteria. We incubated Synechococcus and Prochlorococcus under present-day (380 ppm) or predicted year-2100 CO2 levels (750 ppm), and under normal versus elevated temperatures (+4°C) in semicontinuous cultures. Increased temperature stimulated the cell division rates of Synechococcus but not Prochlorococcus. Doubled CO2 combined with elevated temperature increased maximum chl a–normalized photosynthetic rates of Synechococcus four times relative to controls. Temperature also altered other photosynthetic parameters (α, Φmax, Ek, and ) in Synechococcus, but these changes were not observed for Prochlorococcus. Both increased CO2 and temperature raised the phycobilin and chl a content of Synechococcus, while only elevated temperature increased divinyl chl a in Prochlorococcus. Cellular carbon (C) and nitrogen (N) quotas, but not phosphorus (P) quotas, increased with elevated CO2 in Synechococcus, leading to ∼20% higher C:P and N:P ratios. In contrast, Prochlorococcus elemental composition remained unaffected by CO2, but cell volume and elemental quotas doubled with increasing temperature while maintaining constant stoichiometry. Synechococcus showed a much greater response to CO2 and temperature increases for most parameters measured, compared with Prochlorococcus. Our results suggest that global change could influence the dominance of Synechococcus and Prochlorococcus ecotypes, with likely effects on oligotrophic food-web structure. However, individual picocyanobacteria strains may respond quite differently to future CO2 and temperature increases, and caution is needed when generalizing their responses to global change in the ocean.