Currently, atovaquone is not recommended for treating severe Pneumocystis jirovecii pneumonia (PCP) due to insufficient evidence in clinical studies. This report describes a case of severe PCP in a human immunodeficiency virus (HIV)-negative immunosuppressed patient who was successfully treated with oral atovaquone and corticosteroids. A 63-year-old Japanese woman complained of fever and dyspnea for 3 days. She had been treated with oral prednisolone (30 mg/day) for interstitial pneumonia for 3 months without PCP prophylaxis. Although we could not confirm P. jirovecii from the respiratory specimen, a diagnosis of PCP was indicated by marked elevation of serum beta-D-glucan levels and bilateral ground-glass opacities in the lung fields. Based on the arterial blood gas test results (alveolar-arterial oxygen difference >45 mmHg), the disease status of PCP was defined as severe. Trimethoprim-sulfamethoxazole (SXT) is the first-line drug for treating severe PCP. However, given the patient's history of SXT-induced toxic epidermal necrolysis, she was administered atovaquone instead of SXT. Her clinical symptoms and respiratory condition gradually improved, with a 3-week treatment showing a good clinical course. Previous clinical studies on atovaquone have only been conducted in HIV-positive patients with mild or moderate PCP. Accordingly, the clinical efficacy of atovaquone for severe PCP cases or PCP in HIV-negative patients remains unclear. There is a rising incidence of PCP among HIV-negative patients, given the increasing number of patients receiving immunosuppressive medications; moreover, atovaquone has less severe side effects than SXT. Therefore, there is a need for further clinical investigation to confirm the efficacy of atovaquone in cases of severe PCP, especially among HIV-negative patients. In addition, it also remains unclear whether corticosteroids are beneficial for severe PCP in non-HIV patients. Thus, the use of corticosteroids in cases of severe PCP in non-HIV patients should also be investigated.