Background <p>The COVID-19 pandemic has triggered many social crises, and the sudden change in life circumstances has resulted in extremely challenging levels of mental health among adolescents. High levels of perceived stress coincided with low levels of life satisfaction, with self-efficacy and meaning in life possibly playing a role. This study explores the relationship between perceived stress and life satisfaction among Chinese adolescents during the COVID-19 pandemic. Self-efficacy and meaning in life were investigated as two mediating factors for this relationship.</p> Methods <p>2045 students from three middle schools in Chongqing completed the Perceived Stress Scale (PSS), Satisfaction With Life Scale (SWLS), General Self-efficacy Scale (GSES) and Meaning in Life Questionnaire (MLQ). Process Macro model 6 was used to test the chain mediation between variables.</p> Results <p>① Perceived stress was significantly negatively related to life satisfaction, self-efficacy, and meaning in life; life satisfaction, self-efficacy, and meaning in life were significantly positively related; ② Self-efficacy and meaning in life chain-mediated between perceived stress and life satisfaction.</p> Conclusions <p>During the COVID-19 pandemic, perceived stress is an important factor affecting adolescent life satisfaction. Perceived stress not only directly affects life satisfaction, but also indirectly affects it through reduced self-efficacy and meaning in life. Primary and secondary schools and psychological centers can start with self-efficacy and meaning in life training in order to enhance the mental health of young people, alleviate perceived stress and improve their life satisfaction.</p>