A 2-month-old infant Hispanic female with failure to thrive and choking episodes was admitted with progressive worsening of respiratory effort, paroxysmal coughing, and hypoxemia. She required prolonged mechanical ventilation and post-pyloric feeding for concern of aspiration with no marked improvement of chest radiogram or CT findings. Lung biopsy performed and remarkable for lymphocytic infiltration but without a definite diagnosis. Genetic testing identified a unique heterozygous mutation in the COPA gene. She was started on rituximab and azathioprine initially and has weaned off oxygen and the ventilator. We report a unique case of interstitial lung disease secondary to COPA gene mutation without frank pulmonary hemorrhage, renal, or joint involvement upon initial presentation.