Background Systemic inflammation has been implicated in the development of cognitive dysfunction following carotid endarterectomy (CEA). Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. We hypothesize that patients with elevated preoperative NLR have increased risk of cognitive dysfunction 1 day after CEA. Methods Five hundred fifty-one patients scheduled for CEA were enrolled at Columbia University in New York, NY from 1995 to 2012. NLR was retrospectively reviewed; only 432 patients had preoperative NLR values available within 2 weeks of CEA. NLR was analyzed as a continuous variable and categorically with a cutoff of ≥5 and <5 and equal tertiles, as done in previous studies. Results Patients with cognitive dysfunction had significantly higher NLR than those without cognitive dysfunction (4.5 ± 4.0 vs 3.2 ± 2.6; P  < .001). The incidence of cognitive dysfunction was significantly higher in patients with NLR ≥5 than NLR <5 (34.7% vs 12.8%; P  < .001). Significantly fewer patients in the low tertile had cognitive dysfunction than in the high tertile (6.9% vs 25.9%; P  <.001) and middle tertile (6.9% vs 17.4%; P  = .006). In the final multivariate model, diabetes mellitus (odds ratio OR, 2.03; 95% confidence interval CI, 1.08-3.75; P  = .03) and NLR ≥5 (OR, 3.38; 95% CI, 1.81-6.27; P  < .001) were significantly associated with higher odds of cognitive dysfunction, while statin use was significantly associated with lower odds (OR, 0.48; 95% CI, 0.27-0.84; P  = .01). Conclusions Preoperative NLR is associated with cognitive dysfunction 1 day after CEA. NLR ≥5 and diabetes mellitus are significantly associated with increased odds of cognitive dysfunction whereas statin use is significantly associated with decreased odds.