Purpose: To study whether a clinically significant increase in intraocular pressure (IOP) occurs during simulated sleep conditions with the subject's head turned comfortably into a pillow (the simulated sleep position) and the effect of protective glasses on any such IOP rise. Methods: A specially developed electronic epipalpebral pressure (EPP) sensor was attached to an eyelid of the right eye of all participants: 11 patients with primary open-angle glaucoma and 11 healthy volunteers. During calibration, mechanical pressure was applied to the EPP sensor taped to the lower eyelid and the IOP was measured simultaneously at the slit lamp by Goldmann applanation tonometry. The EPP was increased in a stepwise fashion to assess the relationship between EPP and IOP for each individual eye. Thereafter, EPP (with the sensor now taped to the upper eyelid) measurements were performed in the simulated sleep position, both with and without protective glasses. The EPP was determined in each individual eye, and the estimated IOP was then inferred from the established EPP/IOP relationship. Results: In the simulated sleep position, the mean IOP increased by an estimated 19.6 mmHg (SD: 7.5; range 11.6–32.8; p < 0.0001) in the patient group and 28.0 mmHg (SD: 9.6; range 12.3–41.1); p < 0.0001) in the control group. When the subjects wore protective glasses, the mean estimated IOP decreased again by 16.3 mmHg (SD: 5.6; range 9.8–28.1; p < 0.0001) in the patient group and 25.1 mmHg (SD: 8.2; range 11.7–38.3; p = <0.0001) in the control group. Conclusion: Turning the head into a pillow gave a large and clinically significant increase in the estimated IOP in the simulated sleep position. With protective glasses, however, the increase in estimated IOP was almost absent. Therefore, protective shielding of the eyes during sleep may be a treatment option in glaucoma.