Objective Depression is a common consequence after stroke and has become a significant issue in clinical practice and research. The aim of this study was to explore associated factors of post-stroke depression among first-ever stroke patients in Hong Kong. Methods A longitudinal study was conducted to collect data in face-to-face interviews and by physical assessment at two time points: T1, within 48 hours of admission to a rehabilitation hospital; and T2, 6 months after the first interview. T2 interviews and assessments were conducted in the participant’s current place of residence. Participants were first-ever stroke patients in Hong Kong. Post-stroke depression was measured using the Center of Epidemiological Study-Depression (CES-D) Scale. Backward linear regression analysis was performed to examine factors associated with level of post-stroke depression at T2. Results Our findings showed that 69% of participants exhibited clinically relevant levels of depressive symptoms at T1 and 48% at T2. Regression analysis revealed complex relationships between the level of depressive symptoms, demographic characteristics and variations in perceived levels of social support. Five variables were found to explain 55% of the variance in depressive symptoms at T2. The variables with significant standardized regression coefficients (β) were: companionship (P=0.001), informational support (P=0.025), baseline level of depressive symptoms (Plt;0.001), ADL dependence level (Plt;0.001) and being a homemaker before the stroke (P=0.039). Conclusions We have followed a group of stroke patients over a 6-month period. Our findings suggest that when screening for post-stroke depression, health professionals must take into consideration of the clinical, socio-personal characteristics that might increase a stroke patient’s vulnerability to develop depression after stroke.