Melanopic stimuli trigger diverse non-image-forming effects. However, evidence of a melanopic contribution to acute effects on alertness and performance is inconclusive, especially under common lighting situations. Effects on cognitive performance are likely mediated by effort-related physiological changes. We assessed the acute effects of lighting in three scenarios, at two times of day, on effort-related changes to cardiac contraction as indexed by the cardiac pre-ejection period (PEP). In a within-subject design, twenty-seven participants performed a cognitive task thrice during a morning and a late-afternoon session. We set the lighting at 500 lux in all three lighting scenarios, measured horizontally at the desk level, but with 54 lux, 128 lux, or 241 lux melanopic equivalent daylight illuminance at the eye level. Impedance cardiography and electrocardiography measurements were used to calculate PEP, for the baseline and task period. A shorter PEP during the task represents a sympathetic heart activation and therefore increased effort. Data were analysed with linear mixed-effect models. PEP changes depended on both the light scene and time of day (p = 0.01 and p = 0.002, respectively). The highest change (sympathetic activation) occurred for the medium one of the three stimuli (128 lux) during the late-afternoon session. However, effect sizes for the singular effects were small, and only for the combined effect of light and time of day middle-sized. Performance scores or self-reported scores on alertness and task demand did not change with the light scene. In conclusion, participants reached the same performance most efficiently at both the highest and lowest melanopic setting, and during the morning session. The resulting U-shaped relation between melanopic stimulus intensity and PEP is likely not dependent solely on intrinsic ipRGC stimuli, and might be moderated by extrinsic cone input. Since lighting situations were modelled according to current integrative lighting strategies and real-life indoor light intensities, the result has implications for artificial lighting in a work environment.