Impaired decision-making skills in patients with cocaine addiction are thought to drive both initiation and continuation of cocaine use despite its negative consequences. Literature suggests that females advance more quickly into substance use disorder, indicating sex-differences in vulnerability to drug addiction. The gambling task literature in patients addicted to cocaine and in rodents is inconsistent, and sex differences, if sex was not considered as a biological variable may have contributed to this. We hypothesize that chronic cocaine-exposure might affect decision-making in male and female mice differently. Understanding and appreciating these sex-differences might help in developing therapeutic strategies that are effective in females, as treatment outcomes are often poorer in females. To investigate potential sex-differences in decision-making, male and female C57BL/6JRj mice were pre-trained in touchscreen operant chambers to touch the screen for food rewards. The mice then received cocaine or saline injections for 21 days. Starting from the first day of cocaine withdrawal, they were tested in a mouse gambling task, where mice chose amongst four options (safe, optimal, uncertain and risky), each associated with different magnitudes and probabilities of reward (vanilla-flavoured nutridrink food reward) and punishment (time outs) in one-hour sessions. The effect of cocaine exposure was sex-dependent; male mice that were exposed to cocaine developed a more optimal decision-making strategy than controls and female mice in the cocaine group seemed to develop preference for the optimal choice slower than controls during cocaine “abstinence.” Thus, chronic cocaine exposure affected decision-making in male and female mice differently.