Objective To investigate the correlation of red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) with total imaging load of cerebral small vessel disease (CSVD), and the clinical diagnostic value of RDW, NLR and their combined indicators for high load of CSVD imaging. Methods The medical records of CSVD patients hospitalized in the Department of Neurology of Baotou Central Hospital between October 2018 and October 2022 were retrospective collected. The total imaging load of CSVD was obtained by evaluating the cranial MRI and divided into a low load group and a high load group. The general clinical data, past medical history, and blood biochemical indicators were compared between the two groups. The correlation analysis method was used to analyze the relationship between the relevant indicators and the total imaging load. Logistic regression analysis was used to analyze the risk factors of the total imaging load of CSVD. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of the detection indicators for clinical diagnosis. Results A total of 320 patients were included. Among them, there were 201 cases (62.81%) in the low load imaging group and 119 cases (37.19%) in the high load imaging group. Excepted for age, gender, history of hypertension, RDW, and NLR (P<0.05), there was no statistically significant difference in the comparison of other indicators between the two groups (P>0.05). Spearman correlation analysis showed that RDW (r=0.445, P<0.001) and NLR (r=0.309, P<0.001) were positively correlated with the total imaging load of CSVD. The results of multivariate logistic regression analysis showed that age, male gender, RDW, and NLR were risk factors for high imaging load of CSVD. The areas under the ROC curve of RDW, NLR, and their combined indicators were 0.733, 0.644, and 0.792, respectively.Conclusions In patients with CSVD, the levels of RDW and NLR are related to the total imaging load of CSVD, which are independent risk factors for high imaging load of CSVD. The levels of RDW and NLR have clinical diagnostic value in predicting CSVD high load.