We investigated the possible associations between postoperative delirium (POD) and routinely available preoperative inflammatory markers in patients undergoing lumbar spinal fusion surgery (LSFS) to explore the role of neuroinflammation and oxidative stress as risk factors for POD. We analyzed 11 years’ worth of data from the Smart Clinical Data Warehouse. We evaluated whether preoperative inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the CRP-to-albumin ratio (CAR), affected the development of POD in patients undergoing LSFS. Of the 3081 subjects included, 187 (7.4%) developed POD. A significant increase in NLR, MLR, and CAR levels was observed in POD patients (p < 0.001). A multivariate analysis showed that the second, third, and highest quartiles of the NLR were significantly associated with the development of POD (adjusted OR (95% CI): 2.28 (1.25–4.16], 2.48 (1.3–4.73], and 2.88 (1.39–5.96], respectively). A receiver operating characteristic curve analysis showed that the discriminative ability of the NLR, MLR, and CAR for predicting POD was low, but almost acceptable (AUC (95% CI): 0.60 (0.56–0.64], 0.61 (0.57–0.65], and 0.63 (0.59–0.67], respectively, p < 0.001). Increases in preoperative inflammatory markers, particularly the NLR, were associated with the development of POD, suggesting that a proinflammatory state is a potential pathophysiological mechanism of POD.