Mobilization of critically ill patients within 72 hours of admission is associated with improved outcomes. Recently, the predictive value of regional cerebral oxygen saturation (rSO2) measured via near-infrared spectroscopy (NIRS) has been emphasized. This study aimed to evaluate the differences in rSO2 values depending on the availability of mobilization within 72 hours in the ICU. Eighty patients admitted to the emergency center between June 2020 and December 2022 were analyzed. Patients were assessed based on whether they could be mobilized within 72 hours (early mobilization group, EM) or later (non-early mobilization group, non-EM). During mobilization, prefrontal rSO2 values were monitored. Regarding patient background, significant differences were noted between the groups, including delayed release in non-EM patients. rSO2 values varied significantly, with the lowest values in the first half of end-sitting in both groups (non-EM 56.5 ± 4.8%, EM 58.6 ± 4.3%, p < 0.05). The rSO2 value was also lower in the non-EM group than in the EM group (P < 0.014). A weak correlation was observed between rSO2 and the number of days to first mobilization (r = −0.251, p = 0.025). The rSO2 value may serve as a potential marker to guide the timing of mobilization in ICU patients.