Background: Sleep deprivation (SD) has emerged as a significant public health concern because of its adverse effects on cognition and behavior. However, the influence of circadian rhythms on SD and brain activities has been less studied. This study employed functional magnetic resonance imaging (fMRI) and functional connectivity density (FCD) metrics to investigate the interaction between sleep pressure and circadian rhythms during SD. Methods: Thirty-six volunteers with good sleep habits underwent a sleep deprivation trial. Sleepiness was assessed using the Stanford Sleepiness Scale (SSS) at multiple time points, and fMRI scans were conducted to derive global and local FCD (gFCD and iFCD) values. This study focused on specific brain regions and networks, including the thalamus, the frontoparietal network (FPN), and the default mode network (DMN). Results: Analysis indicated significant changes in gFCD and iFCD values in several key brain regions. A strong correlation was found between sleepiness and both gFCD and iFCD values in certain areas, such as the left superior temporal gyrus and left thalamus. The gFCD values in these regions showed a gradual increase across sessions, while iFCD values in the right superior frontal gyrus decreased. Conclusions: This study revealed that SD leads to enhanced functional activities in the DMN and thalamus and decreased activity in the FPN. These changes in brain activity were significantly correlated with increases in sleepiness, as measured by the SSS. Our findings underscore the importance of understanding the neural underpinnings of SD and could guide future clinical interventions aimed at mitigating its effects.