Pharmaceutical compounds are continuously released into the aquatic environment, resulting in their ubiquitous presence in many estuarine and coastal systems. As pharmaceuticals are designed to produce effects at very low concentrations and target specific evolutionary conserved pathways, there are growing concerns over their potential deleterious effects to the environment and specifically to aquatic organisms, namely in early life-stages. In this context, the long-term effects of exposure of juvenile meagre Argyrosomus regius to three different pharmaceuticals were investigated. Fish were exposed to environmental concentrations of one of three major used pharmaceuticals: the antidepressant fluoxetine (0.3 and 3 µg/L for 15 days), the anti-hypertensive propranolol and the non-steroidal anti-inflammatory agent diclofenac (0.3 and 15 µg/L for 30 days). Pharmaceuticals bioconcentration in fish muscle was examined, along with biomarkers in different tissues related with antioxidant and biotransformation responses (catalase, superoxide dismutase, ethoxyresorufin-O-deethylase and glutathione S-transferase), energetic metabolism (lactate dehydrogenase, isocitrate dehydrogenase and electron transport system activities), neurotransmission (acetylcholinesterase activity) and oxidative damage (DNA damage and lipid peroxidation levels). Overall, each pharmaceutical had different potential for bioconcentration in the muscle (FLX > PROP > DCF) and induced different biological responses: fluoxetine was the most toxic compound to juvenile meagre, affecting fish growth, triggering antioxidant defense responses, inhibiting detoxification mechanisms and increasing lipid peroxidation and DNA damage in the liver; propranolol exposure increased DNA damage and decreased aerobic metabolism in fish muscle; and diclofenac showed no potential to bioconcentrate, yet it affected fish metabolism by increasing cellular energy consumption in the muscle and consequently reducing fish net energy budget. The diverse response patterns evidence the need for future research focused on pharmaceuticals with different modes of action and their exposure effects on organismal physiological mechanisms and homeostatic status. Ultimately, the combination of sub-individual and individual responses is key for ecologically relevant assessments of pharmaceutical toxicity