We evaluated the usefulness of preoperative neutrophil–lymphocyte count ratio (NLCR) in predicting postoperative sepsis after percutaneous nephrolithotomy (PCNL). In total, 487 patients who underwent PCNL for renal stones were included in the present retrospective study. The stone burden, number of tracts and location, operation time, fluoroscopy time, presence of residual stones, and blood transfusion rates were postoperatively recorded in all patients. All patients were followed up for signs of systemic inflammatory response syndrome (SIRS) and sepsis. The association of sepsis/SIRS with the risk factors of infectious complications, including NLCR, was evaluated. SIRS was detected in 91 (18.7%) patients, 25 (5.1%) of whom were diagnosed with sepsis. Stone burden, operation time, irrigation rate, previous surgery, nephrostomy time, access number, blood transfusion, residual stone, postoperative urinary culture, renal pelvis urinary culture, and stone culture were found to be predictive factors for SIRS and sepsis development. Receiver operating characteristic curve analysis revealed an NLCR cutoff of 2.50 for predicting the occurrence of SIRS/sepsis. We found that the incidence of sepsis was significantly higher in patients with NLCR ≥ 2.50 than in patients with NLCR < 2.50 (p = 0.006). Preoperative and postoperative urine culture positivity were associated with high NLCR (p = 0.039 and p = 0.003, respectively). We believe that preoperative NLCR may be a promising additive predictor of bacteremia and postoperative sepsis in patients who undergo PCNL for renal stones. This marker is simple, easily measured, and easy to use in daily practice without extra costs.