Background: The impact of interleukin-6 receptor inhibitors (IL6ri) on Coronavirus disease 2019 (Covid-19) outcomes remains uncertain. Methods: Patients with severe and critical Covid-19 were given an IL6ri (sarilumab or tocilizumab) based on pragmatic and iteratively reviewed guidelines at a safety net hospital with a diverse population. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients requiring >4 liters/minute of oxygen or having an alveolar-arterial gradient >50 mmHg and elevated inflammatory markers (C-reactive protein >100 mg/L or lactate dehydrogenase >450 units/L). Patients were divided into 2 groups, those requiring ≤ 45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. Main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Findings: Prior to treatment, 255 consecutive Covid-19 patients treated with IL6ri (149 stage IIB and 106 stage III) had hypoxemia requiring supplemental oxygen and had elevated inflammatory markers. Patients treated in stage IIB had lower mortality than the stage III group (adjusted hazard ratio [aHR]: 0.20; 95% confidence interval [CI] 0.07-0.60). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR: 2.04; 95% CI 1.53 – 2.73) and to have intubation-free survival (HR: 0.39; 95% CI: 0.20-0.74). Interpretation: Our finding that early IL6ri were associated with reduced mortality from severe Covid-19 can guide current clinical management while we await definitive results from randomized controlled trials. Funding Statement: This work was supported by National Institutes of Health grants K24-AI145661 and 5T32AI052074-13. Declaration of Interests: None to declare Ethics Approval Statement: All activities associated with this project were approved by the Boston University Medical Center Institutional Review Board (IRB)