Metabolism is a set of chemical reactions in an organism that provide energy and enable growth and knowledge about its function provides valuable information on the species researched. The aim of this paper was to investigate the physiological response of Noah's ark, Arca noae and bearded horse mussel, Modiolus barbatus to different salinity values, the amount of food and the size of the individual. The oxygen consumption, ammonia excretion, atomic oxygen and nitrogen ratio (O: N) and clearance rate were investigated. Although these species are often explored, very little information has been published about their physiological responses to stress. The study was conducted in the Mali Ston Bay in the period from April 2014 to June 2016. There was a statistically significant difference in the consumption of oxygen of Noah' Ark shell due to different salinity values of seawater and considering the different sizes of test organisms. In the oxygen consumption of bearded horse mussel, a statistically significant difference was observed with respect to feeding time and to different sizes of individuals. There was a statistically significant difference in the excretion of the ammonia of Noah' Ark shell due to the different values of seawater salinity, given the different amount of food, time of feeding and the different size of the individual. In bearded horse mussel different values of seawater salinity do not significantly affect the excretion of ammonia, a statistically significant difference occurs with respect to exposure time to salinity, different amount of food and feeding time. Different sizes of experimental animals, change of food quantity and feeding time statistically significantly affect the O:N ratio of bearded horse mussel and Noah' Ark shell. Differences in the clearance rate in both species were recorded in terms of salinity, feeding time and the size of the individual. Exposure time to different salinity has a greater impact on the Noah' Ark shell. The results show the physiological response of bivalve molluscs to changed conditions where the bearded horse mussels respond better to stress. Seasonal research could provide a more detailed description of the longer-lasting relationship between these species and the environment.