Routine blood examination is an easy way to examine infectious diseases. This study is aimed to develop a model to diagnose serious bacterial infections (SBI) in ICU neonates based on routine blood parameters. This was a cross-sectional study, and data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III). SBI was defined as suffering from one of the following: pyelonephritis, bacteraemia, bacterial meningitis, sepsis, pneumonia, cellulitis, and osteomyelitis. Variables with statistical significance in the univariate logistic regression analysis and log systemic immune–inflammatory index (SII) were used to develop the model. The area under the curve (AUC) was calculated to assess the performance of the model. A total of 1,880 participants were finally included for analysis. Weight, haemoglobin, mean corpuscular volume, white blood cell, monocyte, premature delivery, and log SII were selected to develop the model. The developed model showed a good performance to diagnose SBI for ICU neonates, with an AUC of 0.812 (95% confidence interval (CI): 0.737–0.888). A nomogram was developed to make this model visualise. In conclusion, our model based on routine blood parameters performed well in the diagnosis of neonatal SBI, which may be helpful for clinicians to improve treatment recommendations.