<b><i>Background:</i></b> Light interventions typically exert their mood-related effects during morning bright light exposures over several weeks. Evidence about immediate ambient room light effects on depressed individuals is still sparse. <b><i>Objective:</i></b> The present study aimed at examining the acute effects of a single moderately bright room light exposure on mood, and behavioural and cardiac stress reactions of mildly depressed geriatric inpatients during a short cognitive stimulation and while resting. <b><i>Methods:</i></b> Twenty-one inpatients were tested in a balanced cross-over design on 2 consecutive days under either conventional room light (standard light) or artificial sunlight conditions for 30 min. Room illumination was implemented with an artificial skylight, which perfectly imitated solar indoor illumination (e.g., cloudless sky and bright artificial sun). Light-induced changes of mood, heart rate, and heart rate variability were recorded while performing a perseveration test (acted as cognitive stimulation) twice. Additionally, light-related behaviour was observed during a resting period between the cognitive tests and various subjective ratings were obtained. <b><i>Results:</i></b> Compared to standard light, exposure to artificial sunlight had a subjective calming effect over time (p = 0.029) as well as decreased heart rate and increased vagal tone (root mean squared of successive inter-beat intervals), both under cognitive workload and in resting conditions. Effect sizes of reported cardiac reactions were large. Cognitive variables were not influenced by light. Additionally, under the higher corneal illuminance of the artificial sunlight, patients perceived stronger glare (p = 0.030) and kept their eyes closed for longer times (p = 0.033) during the resting period. However, patients did not avoid bright light exposure while resting but voluntarily stayed within the area directly lit by the artificial sun nearly all the time (97%). <b><i>Conclusion:</i></b> To our knowledge, this study for the first time demonstrated immediate psychophysiological effects of a single, short room light exposure in mildly depressed geriatric inpatients during a short cognitive stimulation and while resting. The findings complement reported evidence on immediate alerting and mood-related effects of bright light exposures.