Aims:General psychosocial stress and job strain have been related to blood pressure (BP) with conflicting results. This study sought to explore the contribution of several lifestyle factors in the relation between general psychosocial stress, job strain and BP.Methods:This cross-sectional study investigated the association of general stress and job strain with systolic BP (SBP) and diastolic BP in a sample of 9441 employed individuals from the EpiHealth cohort. General stress was measured by the Perceived Stress Scale. Job strain was assessed with the Job Content Questionnaire, assessing two dimensions of job strain: psychological job demand and decision latitude. Linear regression and sensitivity analysis were performed.Results:At the uncorrected model, general stress, job demand and decision latitude were all inversely associated with SBP. After further adjustment for lifestyle and health parameters, only general stress was associated with SPB (β coefficient: −0.103; 95% confidence interval −0.182 to 0.023).Conclusions:General stress is associated with lower SBP independently of lifestyle in middle-aged adults. Our findings point towards a major contribution for job-unrelated stressors in determining SBP and support the pivotal role of lifestyle behaviours and health status in modulating the effect of stress on BP, calling for a careful selection of confounders.