The combined effects of the abiotic factors such as temperature and synthetic progestins on the biochemical and physiological performances of marine clam Ruditapes decssatus under sub-chronic conditions are poorly studied. Here, we investigated the effects of levonorgestrel (1000 ng/l) alone or combined with increasing temperature of 20, 24 and 28°C on the biochemical and physiological responses and the gonad histology of the clam (Ruditapes decussatus) for 28 days. Our results revealed that, in clams treated with levonorgestrel (LNG) alone, there was an impairment of the defense against oxidative stress related to the inductions of CAT, GST and PSH, a reduction in the lysosomal membrane stability, a physiological disturbance via an increase in the level of estradiol, a decrease in the number of gonad oocytes and a reduction in vitellogenin like protein. Furthermore, exposure to heat stress of 20°C, 24°C and 28°C, alone or in combination with LNG, enhanced SOD antioxidant activity which was ineffective in preventing lipoperoxidation and altered clam’s physiological processes of reproduction via dramatic reduction of gonad oocyte numbers and of vitellogenin like protein reserves. Overall, these findings can be taken as a warning sign of temperature and levonorgestrel progestin effect that can lead to effective changes in the structure and function of target vital organs, such as the gonads of the clam Ruditapes decussatus, and this may have implications for the whole organism and populations.