Abstract The disruption of cortical assembly activity has been associated with anesthesia-induced loss of consciousness. However, information about the relationship between cortical assembly activity and the variations in consciousness associated with natural vigilance states is currently lacking. To address this, we performed vigilance state-specific clustering analysis on 2-photon calcium imaging data from sensorimotor cortex in combination with global EEG microstate analysis derived from multi-EEG signals obtained from widespread cortical locations. Our analysis revealed no difference in the structure of assembly activity during quiet wakefulness (QW), NREMs, or REMs, despite the latter two vigilance states being associated with significantly reduced levels of consciousness relative to QW. However, we found a significant coordination between global EEG microstate dynamics and local cortical assembly activity during periods of QW, but not sleep. These results suggest that the coordination of cortical assembly activity with global brain dynamics could be a key factor of sustained conscious experience.