To evaluate the clinical significance of NRBCs in the peripheral blood of critically ill patients admitted to the ICU to find a cut-off to predict mortality. A cross-sectional study was carried out over a period of six months September 1, 2020, to March 31, 2021, in Lahore, Pakistan. A totalof 800 critically ill patients of both sexes in the age group of 18-70 years were included. Patients younger than 18 years and patients who underwentsurgery were excluded. A quantity of 3 ml of whole blood sample in an ethylenediamine tetraacetic acid (EDTA) vial from each patient was run on SYSMEX XN-9000 (Sysmex Corporation, Kobe, Hyogo, Japan) and the results were reviewed on peripheral smears. The incidence of NRBCs in ICU-admitted patients was 62.5% (500/800). The total number of NRBC-positive patients recovering after the treatment was 364 (72.8%). The overall mortality of NRBC-positive patients was 30% (150/500). It was significantly higher (p<0.001) than that of NRBC-negative patients (14%; 44/300).During treatment, the highest mortality rate was seen in patients due to malignancy (100%), followed by sepsis (58.8%). It was observed that the disease pattern and number of NRBCs were significantly different (p<0.001) among all disease groups. However, there was no statistically significant difference in NRBCs on the basis of gender (p >0.05). In our study, a cutoff of NRBCs of 2.50 showed a high risk of mortality with a sensitivity of 91%. The presence of NRBCs may predict mortality in critically ill ICU-admitted patients. Their presence in the blood may be regarded as a marker of severity suggesting a high risk of ICU death.