A retinal subsensitivity to environmental light may trigger Seasonal Affective Disorder (SAD) under low wintertime light conditions. The main aim of this study was to assess the responses of melanopsin-containing retinal ganglion cells in participants (N= 65) diagnosed with unipolar SAD compared to controls with no history of depression. Participants attended a summer visit, a winter visit, or both. Retinal responses to light were measured using the post-illumination pupil response (PIPR) to assess melanopsin-driven responses in the non-visual light input pathway. Linear mixed-effects modeling was used to test a group*season interaction on the Net PIPR (red minus blue light response, percent baseline). We observed a significant group*season interaction such that the PIPR decreased from summer to winter significantly in the SAD group while not in the control group. The SAD group PIPR was significantly lower in winter compared to controls but did not differ between groups in summer. Only 60% of the participants underwent an eye health exam, although all participants reported no history of retinal pathology, and eye exam status was neither associated with outcome nor different between groups. This seasonal variation in melanopsin driven non-visual responses to light may be a risk factor for SAD, and further highlights individual differences in responses to light for direct or indirect effects of light on mood.