Recognizing the growing importance of optimizing work environments for better cognitive performance, this study examined the relationships between general office lighting, psychophysiological responses and cognitive performance. Sixteen healthy adults in their 20s participated in experiments under nine different lighting conditions combining three levels of correlated color temperature (i.e., 4,000K, 5,000K, and 6,500K) and three levels of illuminance (i.e., 200 lx, 500 lx, and 800 lx). In the experiments, subjects’ primary and complex cognitive performances were measured and their psychophysiological responses such as mental workload, drowsiness, mental fatigue and stress, and visual fatigue were evaluated. Statistical analyses revealed that higher correlated color temperature and illuminance significantly enhanced primary cognitive performance but did not significantly impact complex cognitive performance or most psychophysiological responses. Notably, psychophysiological responses and cognitive performances were found to have mutual relationships rather than one being an absolute independent variable for another. The study suggests that tailored smart lighting systems could enhance cognitive performance in office environments by dynamically adjusting lighting conditions based on real-time psychophysiological feedback.