Background Soidum ion balance is one of the most important factor in status of preterm infant. However, the difference in sodium ion level between their results is often exceeds the permissible limit clinically. We performed a study to identify the clinical factors that cause a first-day-after-birth sodium ion concentration difference between an ABGA (arterial blood gas analyzer) and an auto-analyzer in VLBWI (very low birth weight infant). Methods The arterial blood samples of 174 VLBWIs were collected within 2 hours after birth. This study involved 97 cases of simultaneously collected VLBWI arterial samples. Arterial blood samples were collected simultaneously for measurement. Each sample was divided into two for analysis, one was analyzed via an ABGA using the direct ISE method and the other was analyzed by an auto-analyzer using the indirect ISE method. Results The difference in sodium ion concentration between an ABGA and an auto-analyzer was 5.6±3.4 mmol/L, which exceeded the recommended 4 mmol/L according to the United States Clinical Laboratory Improvement Amendments ( P0.001). A Bland-Altman comparison of sodium ion concentration between an ABGA and an auto-analyzer showed that the limits of agreement ranged from −1.1 to 12.3 ( P0.001). VLBWIs with a difference of 4 mmol/L had a greater percentage of maximum weight loss after birth than those with higher values ( P0.001). The mean arterial pressure was lower in VLBWIs with a difference of ＞4 mmol/L ( P0.001). Adjusted regression analysis showed that a physiologic weight loss exceeding 10% and a mean arterial pressure ＞35 mmHg were independent factors for a sodium ion difference exceeding 4 mmol/L between both methods (odds ratio 9.257 [95%CI 2.688–31.871], P0.001 and odds ratio 3.699 [95%CI 1.295–10.564], P=0.015). Conclusions Mean arterial pressure and maximum physiologic weight loss after birth in VLBWI, are clinical factors that influence a sodium ion concentration difference between an AGBA and an auto-analyzer.