Aim This study aimed to shed light on how serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), and C-reactive protein (CRP) correlate with hemoglobin oxygen saturation percentage (SpO2) and the type of respiratory support received among COVID-19 patients hospitalized in COVID-19 intensive care units. Background The clinical care of patients who suffer from COVID-19 requires knowledge of laboratory findings and the way these findings are linked with the type of respiratory support. Methods This descriptive-analytical study was conducted using data from the clinical records of 31 patients hospitalized in the intensive care unit at 22nd-Bahman Hospital in Khaf, Eastern Iran, during the first half of 2021. The study utilized a checklist developed by the researcher for data collection. The data were analyzed with Kolmogorov-Smirnov, independent t, one-way analysis of variance, and Tukey's post hoc statistical tests in the SPSS-22 statistical package. The significance level was established at p <0.05. Results The mean CRP, LDH, and serum levels of IL-6 were significantly higher in COVID-19 patients with SpO2 <93 than in patients with SpO2 ≥93 (p <0.05). Patients receiving intubation and non-invasive respiratory support exhibited significantly greater serum levels of IL-6, CRP, and LDH than patients receiving other respiratory support (p <0.05). The mean CRP, serum levels of IL-6, and LDH were significantly lower among survivors than those who died (p <0.01). Conclusion Understanding the relationship between the serum levels of IL-6, CRP, LDH, and SPO2 and the type of respiratory support can help predict the management of acute respiratory patients, but this decision-making method based on serum levels should be further investigated. and to be compared with the current methods of management of treatment of acute respiratory patients.