Cell capacity for cytosolic NADPH regeneration by NADP-dehydrogenases was investigated in the leaves of two hybrid poplar (Populus deltoides × Populus nigra) genotypes in response to ozone (O3) treatment (120 ppb for 17 days). Two genotypes with differential O3 sensitivity were selected, based on visual symptoms and fallen leaves: Robusta (sensitive) and Carpaccio (tolerant). The estimated O3 flux (POD0), that entered the leaves, was similar for the two genotypes throughout the treatment. In response to that foliar O3 flux, CO2 assimilation was inhibited to the same extent for the two genotypes, which could be explained by a decrease in Rubisco (EC 22.214.171.124) activity. Conversely, an increase in PEPC (EC 126.96.36.199) activity was observed, together with the activation of certain cytosolic NADP-dehydrogenases above their constitutive level, i.e. NADP-G6PDH (EC 188.8.131.52), NADP-ME (malic enzyme) (EC 184.108.40.206) and NADP-ICDH (NADP-isocitrate dehydrogenase) (EC220.127.116.11). However, the activity of non-phosphorylating NADP-GAPDH (EC 18.104.22.168) remained unchanged. From the 11th fumigation day, NADP-G6PDH and NADP-ME profiles made it possible to differentiate between the two genotypes, with a higher activity in Carpaccio than in Robusta. At the same time, Carpaccio was able to maintain high levels of NADPH in the cells, while NADPH levels decreased in Robusta O3-treated leaves. All these results support the hypothesis that the capacity for cells to regenerate the reducing power, especially the cytosolic NADPH pool, contributes to improve tolerance to high ozone exposure.