In order to assess the response of cocoa trees to drought, changes in water status, gas exchange, leaf carbon isotopic ratio (δ13C), photochemical activity, and leaf N and chlorophyll content during the rainy and dry season were measured in 31 Venezuelan cocoa clones (17 Trinitarios, 6 Criollos, and 8 Modern Criollos) grown in a common garden. Drought caused a 40% decrease in water potential (ψ) in all but the Modern Criollos, and a reduction in net photosynthetic rate (A) and stomatal conductance (gs) without an increase in instantaneous water use efficiency (WUE) in 93% of clones, and an increase in δ13C (long-term WUE) in 74% of clones; these responses suggest differences in tolerance to drought among clones. A positive correlation between A and both gs and leaf N content was found for all genotypes. Leaf N content, chlorophyll content, and photochemical activity were reduced during drought, suggesting that metabolism was also inhibited. The best performance during drought was shown by Modern Criollos with the highest WUE, while five Trinitario clones seemed to be less sensitive to drought, since neither chlorophyll, N, total soluble protein concentration, nor gs changed with drought, indicating that those Trinitario clones, with lower A, have a conservative water use. Modern Criollos showed no reductions in either ψ or gs; A remained unchanged, as did WUE, which was the highest, suggesting that these clones would be more successful in environments with low water availability. Our results indicate large variation in physiological response to drought over a range of parameters, suggesting possible differences in tolerance among clones.