Neuropsychiatric and neurodevelopmental disorders are a heterogeneous group of mental diseases affecting about 1-billion people worldwide. Common alterations are in the processing of social information, but dedicated pharmacological interventions are missing. Serotonin (5HT) is classically associated with the processing of social information. However, the role of 5HT dynamic, the related circuits and their pharmacological manipulation are still understudied. The serotonin transporter (SERT) re-uptakes 5HT after synaptic release and is widely expressed in the serotonergic terminals projecting to the medial prefrontal cortex (mPFC), a fundamental hub of socio-cognitive functions. SERT can be reversed using serotonin-releasing-agents to trigger an exocytotic-independent increase of 5HT. In our study, we used d-Fenfluramine, a clinically approved serotonin-releasing-agent to investigate the role of 5HT on social cognition. Combining novel experimental tasks in mice with calcium and fluorescent neurotransmitter imaging, we show that pharmacologically-induced 5HT promotes prosocial effects, reduces social novelty and impacts the discrimination of low-salient empathic states in mice. Consistently, in fiber photometry experiments d-Fenfluramine efficiently increases 5HT in the mPFC. Here, 5HT modulates somatostatin-expressing interneurons – key neuronal substrates of social cognition - by reducing their activity only during the exploration of the conspecific in a low-salience empathic state. Our results highlight the importance of 5HT and serotonin-releasing-agents in the modulation of different social domains, setting the ground for the development of innovative treatments for neuropsychiatric disorders