BACKGROUND Quality of life (QoL), physical activity (PA) level and psychological profile (PF) of patients with serious mental illness have been neglected during patient’s management OBJECTIVE The purpose of this study was to determine the effect of selected psychotropic drugs on the QoL, PA level and PF of patients with serious mental illness METHODS A cross sectional survey involving one hundred and twenty-four subject [62 Serious Mental Illness (SMI) and 62 apparently healthy subjects as control] using purposive and consecutive sampling respectively .Questionnaires for each of the constructs were administered to the participants for data collation. Analysis of the data was done using non parametric inferential statistics of Mann-Whitney U independent test and Spearman’s rho correlation with alpha level set as 0.05. RESULTS Significant difference was recorded in the QoL (p<0.05) of patient with SMI and apparently healthy psychotropic naive participants. There was a significant correlation between the QoL (p<0.05) and PF of participants with SMI. Participants with SMI had significantly lower QoL than apparently healthy psychotropic naive subject. QoL of the healthy psychotropic naive group was better than those of the participants with SMI. Female participants with SMI had higher PA than their male counterparts CONCLUSIONS Psychological profiles of male participants with SMI were lower than male healthy psychotropic naive participants. Clinicians should take precaution to monitor the QoL, PA level and PF because the constructs are relevant in evaluation of treatment outcome.