Background: Central venous pressure (CVP) monitoring remains in common use as an index of circulatory filling and cardiac preload. Positive end-expiratory pressure (PEEP) in mechanically ventilated patients can affect CVP via increasing intra-thoracic pressure. Critical care nurses should be able to measure the CVP competently and identify the factors affecting its readings. Aim: The current study was conducted to determine the effect of PEEP on the CVP readings in mechanically ventilated patients. Methods: a descriptive design used in this study. A convenient sample of 200 adult critically ill patients of both sex, hemodynamically and respiratory stable, having a central venous catheter (CVC) in place, and attached to a mechanical ventilator and pulse oximeter were included in the study. The patient's baseline CVP was recorded while the patient connected to the mechanical ventilator, then the patients were temporary disconnected from the mechanical ventilator and the CVP measured again without the effect of PEEP. Results: About 40% of the study sample aged 45 to 64 years, 52.5% were males, 50 % suffered from respiratory disorders, and 49% were overhydrated. Eighty eight percent of the study sample was on PEEP levels between 5 to < 10 cmH 2 O. The CVP readings while the patients connected to MV were higher than CVP reading while the patients without PEEP, but these differences were not significant. Conclusion: CVP readings are not significant affected by the PEEP up to 15 cmH 2 O. The CVP can be reliably measured while patients are connected to MV. Recommendations: Measurement of CVP can be obtained while the patient is connected to MV.