Background: Socio-political circumstances, including security, poverty, national wealth, income inequality, social integration and political conflicts, determine population health. Anticipated socio-political developments refer to the perceived improvement/deterioration in these circumstances in the future year. Aims: This study tested relationships between this anticipation and population mental health (probable depression/depressive symptoms and life satisfaction) and the mediation roles of negative personal responses toward socio-political situations (frustration, emotional disturbance, self-efficacy in political involvement, perceived sense of security, and satisfaction about societal ability in fulfilling individuals’ needs) in explaining these relationships. Method: The telephone survey randomly interviewed 420 (59.5% female) adults in Hong Kong. Questionnaire included scales assessing the aforementioned variables. Results: Most participants (71.7%) had pessimistic anticipations over socio-political developments; 11.3% of the participants were classified as having probable depression. Anticipated deterioration in socio-political developments was significantly associated with depressive symptoms and life satisfaction; emotional disturbance, sense of security and need satisfaction were partial mediators of these relationships. Need satisfaction and sense of security showed the strongest mediation effects both for mediations that involved depressive symptoms and life satisfaction. Conclusion: Both politicians’ awareness and mental health promotion are required to alleviate the negative impact of negative socio-political perception on mental health.