BACKGROUND: Following the health restrictions related to the COVID-19 pandemic, about a third of French workers experienced mandatory teleworking during the lockdowns. The objective of this study is to examine the complex relationships between teleworking conditions, depressive symptomatology, and the onset of low back pain (LBP) during France's third lockdown in spring 2021. METHODS: Based on the online CoviPrev survey, 466 workers from the French general population who teleworked at least one day a week during lockdown and were free of LBP at the start of lockdown were included in this study. A conceptual model was developed in which relationships between teleworking conditions, depressive symptomatology, and the onset of LBP were assumed. Structural equation modelling was used to test the model. RESULTS: The model showed that teleworking conditions (both material conditions of teleworking and the amount of telework) have a substantial direct and indirect impact on the onset of LBP. The theoretical model proposed 2 pathways for the effect of the teleworking conditions on the onset of LBP: a direct pathway, of a biomechanical nature, and an indirect pathway, mediated by satisfaction with teleworking conditions and depressive symptoms. CONCLUSIONS: This study suggests that there are complex relationships between teleworking conditions, depressive symptomatology, and the onset of LBP, which are essential to characterize to better understand the chain of determinants for the onset of LBP. They also highlight the importance of good working conditions to reduce the impact of teleworking on health, including the prevention of sedentary behaviours.