We present a case of a patient who presented to the emergency department with symptoms suggestive of a chronic obstructive pulmonary disease (COPD) exacerbation one day after receiving the BNT162b2 COVID-19 booster vaccine. Laboratory studies indicated she was in a state of inflammation, but not infection. Other potential triggers, including cardiac and viral etiologies, were ruled out. To our knowledge, this is the first documented case of a COPD exacerbation following the administration of the BNT162b2 COVID-19 vaccine.