Previous studies have reported high prevalence rates of depressive symptoms or syndromes in subjects with first episode psychosis, but data are lacking on the quality of life (QOL) in these subjects. This cross-sectional study seeks to compare the subjective QOL of these individuals with and without a comorbid depressive syndrome at baseline. Using the Structured Clinical Interview to Diagnose DSM IV-Axis I Disorders, the Scale to Assess Unawareness of Mental Disorders (SUMD), Positive and Negative Syndrome Scale (PANSS), Hamilton Rating Scale for Depression (HAM-D), and the World Health Organization Quality of Life-Bref Scale (WHOQOL-BREF), we evaluated 66 consecutive subjects with first episode schizophrenia spectrum disorders (schizophrenia, schizoaffective and schizophreniform disorders) in our Early Psychosis Intervention Program. We found that subjects with a comorbid depressive syndrome had greater awareness of their mental illness, its social consequences and treatment efficacy, but poorer overall QOL, especially in the physical, psychological health, social relationships and environmental domains. The poorer QOL in subjects with a comorbid depressive syndrome may be explained by the greater degree of insight in these patients and their attributing their troubles to poor health, unsatisfactory social support and negative environment. Alternative explanations are also possible, providing possible foci for psychological support and intervention.