Positive end-expiratory pressure is a crucial mechanical breathing parameter. Intra-abdominal hypertension is well defined as a sustained increase in the intra-abdominal pressure ≥12 mmHg. There are still controversies about mechanical ventilation's effect and use of positive end-expiratory pressure on intra-abdominal pressure. We aimed to delineate the relationship between positive end-expiratory pressure and intra-abdominal pressure in mechanically ventilated patients admitted to the intensive care units of a large tertiary hospital in Upper Egypt. This study was a prospective observational study. The study was conducted at a university hospital from October 2023 to February 2024. The enrolled adult patients were allocated into two groups based on their positive end-expiratory pressure: group I, low pressure (<8 cm H2O) and group II, high pressure (8-10 cm H2O). A total of 120 patients were enrolled, 60 patients in each group. The most commonly encountered diagnoses were pneumonia (32/120, 26.7%) and acute respiratory distress syndrome (ARDS) (31/120, 25.8%), respectively. There was a significant difference between the intra-abdominal pressure mean values of the two patient groups, 18.9 ± 3.3 versus 24.4 ± 5.9 mmHg in the group of low versus high pressure (correlation value of .454, p < .001), respectively. There were highly significant correlations between intra-abdominal pressure categories and the patient groups (correlation value of .495, p < .001). There were 24 (40%) versus 0 (0%) patients of high pressure versus low pressure within the category IV group of intra-abdominal hypertension (>25 mmHg). We observed a significant relationship between positive end-expiratory pressure and intra-abdominal pressure in mechanically ventilated patients. The patient group with high pressure had higher mean values compared with the group with low pressure. The study highlights the importance of closely monitoring intra-abdominal pressure in mechanically ventilated patients who receive positive end-expiratory pressure. Further studies are warranted. The relationship between positive end-expiratory pressure and intra-abdominal pressure is an essential issue in daily critical care nursing clinical practice. Considering the occurrence of multiple organ dysfunction as a result of a non-detected increase in intra-abdominal pressure, critical care nurses should pay attention to measuring this pressure to maintain intra-abdominal pressures that are safe for mechanically ventilated and critically ill intensive care unit patients, thereby preventing these undue effects.