High sedentary behaviour (SB) associates with poorer wellbeing among adults at increased cardiovascular risk. The aim of this study was to investigate the effects of reducing SB on perceived quality of life, depressive symptoms, stress, and workability among physically inactive adults with metabolic syndrome. Sixty-four sedentary, inactive adults [58 (SD 7) years old, 58% women, BMI 32 (4) kg/m²] with metabolic syndrome were randomised into the intervention (n = 33) and control (n = 31) groups. The 6-month intervention aimed at reducing SB by 1 h/day without adding exercise, while the control group kept their usual SB. All participants wore accelerometers throughout the study to monitor SB and physical activity. Health-related quality of life, stress, depressive symptoms and workability were assessed at baseline, at three months, and after the intervention using the RAND-36, perceived stress questionnaire (PSQ), general health questionnaire (GHQ-12), and the workability score. Main intervention effects were analysed using linear mixed models for repeated measurements. The RAND-36 vitality score decreased in the control group [-2.9 (95% CI -7.7, 1.9) and -1.0 (-5.9, 4.0) from baseline to three and six months, respectively] and increased in the intervention group [+5.7 (1.1, 10.4) and +5.3 (0.4, 10.3) from baseline to three and six months, respectively; between-group difference at three months p = 0.012 and at six months p = 0.079]. The PSQ index increased among all participants [+0.03 (-0.01, 0.06) from baseline to six months; time p = 0.033, no significant between-group differences p = 0.143]. Among all participants, the change in SB correlated negatively with the change in RAND-36 social functioning score, and the change in light physical activity correlated negatively with the change in PSQ index. Moreover, the change in SB breaks correlated negatively with the RAND-36 physical and social functioning scores. Aiming to reduce SB by 1 h/day may increase perceived vitality among physically inactive adults with metabolic syndrome.