The aim of this study was to explore associated factors of post-stroke depression (PSD) among Chinese first-time stroke patients. A 6-month prospective design was adopted with data collected by face-to-face interviews and physical assessment at two observation time points: T1, within 48 h of admission to the rehabilitation hospitals and T2, 6 months after the first interview in the subject's current place of residence. The prevalence of PSD at T1 and T2 was found to be 69% and 48% respectively. Backward linear regression showed that five variables explained 55% of the variance of PSD at T2. Participants who had a higher level of depression at T2 tended to have a higher level of functional disability, less social companionship and poorer informational support. Those who had been homemaker at pre-morbid state and those who exhibited a higher level of depressive symptoms at T1 showed a higher level of depression at T2. The results of this study suggest that PSD could be a psychological condition arising from the disabling consequences and altered family roles caused by a stroke.