Background: The standard lumbar puncture position involves maximum flexion of both lumbar and cervical spine. The cerebrospinal fluid opening pressure (CSF_op) is measured in a horizontal position. This study investigated if flexion of hip and neck both separately and simultaneously influence intracranial pressure (ICP) to a clinically relevant extent. Methods: Thirty-nine patients, undergoing invasive ICP monitoring as part of diagnostic work-up, were included. The patients underwent either a vertical postural examination (n = 24) or a horizontal postural examination (n = 15) to examine a varying degree of spine flexion. Results: The vertical examination showed that ICP decreased by 15.2 mmHg when straightening the neck in a sitting lumbar puncture position (n = 24, IQR − 20.1 to − 9.7). In the horizontal examination, ICP increased in all but one patient when changing from supine position to lateral recumbent position (n = 15, median increase of 6.9 mmHg, IQR 3.1 to 9.9). Straightening the hips alone decreased ICP with 0.2 mmHg (n = 15, IQR − 0.5 to 2.0), while straightening the neck alone decreased ICP by 4.0 mmHg (n = 15, IQR − 5.9 to − 1.7). However, when straightening the hip and neck simultaneously ICP decreased by 6.4 mmHg (n = 6, IQR − 9.5 to − 4.4). Conclusions: Neck flexion alone, and neck flexion and hip flexion in combination, has significant confounding influence on ICP. This may cause patients to shift from a normal ICP range to a pathological ICP range, which will potentially affect treatment decisions. Consensus on guidelines for body position including neck and hip flexion measuring CSF_op may be needed.