Objective: Combination therapy with programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors might be viewed as a promising therapeutic strategy for resistant lung cancer, and it is becoming common that a second PD-1/PD-L1 inhibitor might be used following progression on previous PD-1/PD-L1 inhibitor. However, a subgroup of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), that occur as a result of on-target and off-tumor inflammation. Materials and Methods: In this report, we presented a patient with small cell lung cancer who received different PD-1/PD-L1 inhibitors during the course of disease progression. This patient experienced radiation-related pneumonitis, immune-related pneumonitis, as well as concomitant bacterial pneumonia. Results: In particular, this patient developed immune-related pneumonitis with a second PD-1 inhibitor when she had a progressive disease on previous PD-L1 inhibitor. This patient was initially responsive to steroid treatment, but rapidly develop more severe pneumonitis and concomitant bacterial pneumonia with no response to antibiotics and steroid treatment. Finally, this patient got a good clinical response when receiving additional immunosuppressive medications infliximab and mycophenolate mofetil. Conclusions: Patients with a history of radiation-induced pneumonitis and treated with sequential different PD-1/PD-L1 inhibitors have a relative high risk to develop high-grade or steroid-resistant pneumonitis, and additional immunosuppressive medications should be used earlier when severe pulmonary toxicity occurs.