Maintaining intracranial pressure (ICP) below 20-25 mmHg is an important clinical goal in the treatment of patients with traumatic brain injury (TBI). It is well known that the partial pressure of arterial CO2 (PaCO2) can affect cerebral blood flow, cerebral blood volume, and therefore ICP. The end-tidal CO2 (ETCO2) is usually monitored by clinicians as a proxy for PaCO2. We show examples where subclinical fluctuations in ETCO2 are associated with clinically significant fluctuations in ICR. We estimated ICP from past and present values of ETCO2 with a linear estimator. The variance of the ICP residuals was 37 percent of the variance of the ICP signal at frequencies above 0.33 mHz. We suggest that a large proportion of clinically significant ICP fluctuations could be eliminated or reduced if the patients ventilation and CO2 levels were more tightly regulated.