Increasing temperature due to climate change may represent an important factor influencing the physiology of organisms, with potential impacts on the ecosystem, especially to ectotherms, which include most aquatic species that are highly sensitive to environmental temperature changes. However, in nature there is a multitude of factors influencing an organism at a given time with regard to fitness, while single stressor scenarios are far from ecologically relevant scenarios. The interaction of different stressors, biotic and/or abiotic, can have synergistic or antagonistic effects for the organism, which finally can lead to different states of overall fitness and eventually influence the whole population dynamics. Besides the common abiotic factors affecting organisms, biotic factors (such as inter- and intra-species interaction) ought to be considered when assessing organisms’ responses in a given situation, as they are key events affecting organisms’ dynamics. This study focused on the effects of water temperature increase and predation stress (octopus) on the metabolism of an intertidal rock pool fish, the rock goby (Gobius paganellus), while also addressing the potential interaction of these stressors. Groups of individuals were exposed to simulated predation stress, and temperature increase of 1 °C d-1 from 20 °C up to 29 °C, and also to both stressors combined. Treatment groups were compared with control (20 °C). To get a detailed insight on how both stressors affect these organisms, effects at both whole organismal level (growth and respiration) and cellular level (biochemical biomarkers) were estimated. Therefore, growth, energy available (Ea - total lipids, carbohydrates, and protein), energy consumed (Ec – measuring electron transfer system activity), cellular energy allocation (CEA), energy metabolism related enzyme activities (lactate dehydrogenase-LDH and isocitrate dehydrogenase-IDH), detoxification and oxidative stress responses and consequences (glutathione s-transferase-GST, superoxide dismutase-SOD, catalase-CAT, DNA damage, and lipid peroxidation-LPO) in muscle, gill, and liver tissue, considering both short-term exposure and long-term acclimation, were investigated. In addition, oxygen consumption rates of single fish were measured to establish standard and routine metabolic rates of G. paganellus, and the potential influence of simulated predation risk. Results show a growth decline as a result of all treatments compared to control, and also effects on the assessed biochemical parameters for both temperature and predation risk stressors. This leads to the presumption of physiological changes due to these stressors, and at the same time the stressor individual effects and their potential interaction in the biomarkers are highlighted in this work, while the relevance of these findings are discussed concerning real multi-stressor scenarios.