There is not yet a comprehensive view of how the color of light affects the cerebral and systemic physiology in humans. The aim was to address this deficit through basic research. Since cerebral and systemic physiological parameters are likely to interact, it was necessary to establish an approach, which we have termed "systemic-physiology-augmented functional near-infrared spectroscopy (SPA-fNIRS) neuroimaging." This multimodal approach measures the systemic and cerebral physiological response to exposure to light of different colors. In 14 healthy subjects (9 men, 5 women, age: [Formula: see text] years, range: 24 to 57 years) exposed to red, green, and blue light (10-min intermittent wide-field visual color stimulation; [Formula: see text] blocks of visual stimulation), brain hemodynamics and oxygenation were measured by fNIRS on the prefrontal cortex (PFC) and visual cortex (VC) simultaneously, in addition with systemic parameters. This study demonstrated that (i) all colors elicited responses in the VC, whereas only blue evoked a response in the PFC; (ii) there was a color-dependent effect on cardiorespiratory activity; (iii) there was significant change in neurosystemic functional connectivity; (iv) cerebral hemodynamic responses in the PFC and changes in the cardiovascular system were gender and age dependent; and (v) electrodermal activity and psychological state showed no stimulus-evoked changes, and there was no dependence on color of light, age, and gender. We showed that short-term light exposure caused color-dependent responses in cerebral hemodynamics/oxygenation as well as cardiorespiratory dynamics. Additionally, we showed that neurosystemic functional connectivity changes even during apparently stress-free tasks-an important consideration when using any of the hemodynamic neuroimaging methods (e.g. functional magnetic resonance imaging, positron emission tomography, and fNIRS). Our findings are important for future basic research and clinical applications as well as being relevant for everyday life.