The safety of neoadjuvant chemoimmunotherapy before surgery in patients with non–small cell lung cancer (NSCLC) remains unclear in the perioperative stage. We describe a case of a 63‐year‐old man with IIIC stage NSCLC who received neoadjuvant chemoimmunotherapy and radical lobectomy. After the second cycle of pembrolizumab and chemotherapy (paclitaxel + carboplatin), the patient was diagnosed with immunologic enterocolitis and relieved by glucocorticoid therapy. Radical lobectomy of the right upper lobe was then performed. On postoperative day 4 (POD 4), the patient suddenly suffered suffocated wheezing during sleep. Interstitial lung disease was, therefore, identified by chest computed tomography scan. Glucocorticoids and mechanical ventilation were applied and the symptoms were relieved. On POD 10, the patient developed a bronchial fistula and underwent emergent repair surgery. This is the first case of multi‐organs, multi‐time point immune‐related adverse events (irAE) in perioperative NSCLC patients who received neoadjuvant chemoimmunotherapy. Clinicians should be on high alert for signs of irAEs in neoadjuvant chemoimmunotherapy patients, promptly requiring multidisciplinary management.