The COVID-19 pandemic impacted social life by forcing “social distancing”. This measure has not only severely disrupted daily social interactions but has also led to an increase in mental health problems. As a result, understanding the neurobiological mechanisms underlying pathogen threat-induced social avoidance (PTSA) has become increasingly important. Studies in rodents have proved valuable in the investigation of PTSA. Mice, for instance, innately avoid sick conspecifics, although little is known about the specific behavioral and circuit mechanisms underlying this response. We hypothesized that mice would assign a lower reward value to sick conspecifics than healthy ones. In a free social interaction task with either a healthy or a sick conspecific, mice spend less time interacting with sick social stimuli. We then investigated the neural mechanisms underlying this behavioral outcome. In social decision-making, the medial prefrontal cortex (mPFC) exerts top-down control over downstream brain regions, such as the nucleus accumbens (NAc), which translates motivation into action. Therefore, we performed in vivo fiber-optic recordings of mPFC glutamatergic neurons projecting to the NAc (mPFC-to-NAc). We found that mPFC-to-NAc cells are more activated toward sick than healthy conspecifics, conveying a "break" signal to stop social interactions with them. In addition, we found that odor components mainly mediate this signal. Through in vivo optogenetic manipulations, we are currently testing the causal relationship between PTSA and mPFC-to-NAc neuronal activity. Understanding the behavioral and neural mechanisms underlying social-reward value assignment to pathogen threat could help us prevent social isolation-related risks.