Objectives: Evidence for an association between duration of untreated illness (DUI) with clinical and functional outcome or brain volume (change) in schizophrenia patients is inconclusive. We aimed to investigate the relationship between DUI, outcome and brain volume at illness onset or brain volume change during the first five years of the illness in first-episode patients. Methods: Magnetic resonance images were acquired at baseline (T0) and after 5-year (T5) of 57 schizophrenia patients. Correlations were calculated in patients between brain volume (change), DUI and outcome variables. Results: We found no significant correlation between DUI and brain volume (change) in schizophrenia patients. A longer DUI was significantly correlated with higher PANSS scores at T0 and T5, and with higher scores on the Camberwell Assessment of Need scale at T5. Baseline volume of the cerebrum and lateral ventricles, and cerebellum volume (change) were associated with PANSS scores at T0 and T5. Conclusion: Although clinical outcome is associated with both brain volume (change) and DUI, we found no evidence for a relationship between DUI and brain volume (change). DUI and baseline brain volume or 5-year brain volume (change) seem to explain different parts of the variation in clinical outcome.