Background Lipids play numerous functions in lung biology and pathophysiology of infection, in addition to their role in lipid transport, lipoproteins share in innate immunity that is the most important way for the host to defend against microbes. The NLR (neutrophil-lymphocytic ratio) is a good indicator of systemic inflammation and infection. Objective To evaluate the role of cholesterol, lipoproteins, and neutrophilic-lymphocytic ratio in the assessment of patients with pneumonia. Patients and methods This prospective case–control study included 52 subjects; they were categorized into 2 groups. Group A included 42 patients with pneumonia admitted to the Chest Department,Menoufia University, and group B included 10 healthy people during the period from May 2019 to December 2019. History taking, clinical examination, laboratory investigation in the form of CBC and lipid profile, and radiological investigation in the form of CXR and CT chest if needed were done to all subjects of the study. Results The mean cholesterol level in group A was 149.76 ± 42.79 which was statistically significantly lower as compared with group B (165.90 ± 45.50) (p = 0.039). The mean HDL level in group A was 43.16 ± 6.32 which was statistically significantly lower as compared with group B (50.51 ± 9.60) (p = 0.026). No statistically significant difference was found in the triglyceride level, LDL level and VLDL between the subjects in the two studied groups (p = 0.479, 0.792, and 0.606), respectively, but all levels were still within normal levels. Mean NLR in group A was 7.04 ± 7.98 which was statistically significantly higher as compared with group B (3.04 ± 1.6) (p = 0.004). Roc curve of neutrophil–lymphocyte ratio shows that the cutoff point is 1.94 and the N/L ratio had area under curve of 78% with 79.6% sensitivity and 67.8% specificity. Conclusion Serum cholesterol and high-density lipoprotein levels significantly decreased in patients with pneumonia when compared to the control group but were still within normal range. Lipid profile is affected by different variables like smoking index, body mass index, and sex. The neutrophil–lymphocyte at cutoff point is 1.94, and N/L ratio had area under curve of 78% with 79.6% sensitivity and 67.8% specificity. Trial registration TCTR, TCTR20220524001. Registered on 24 May 2022, retrospectively registered.