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The Pfizer-BioNTech COVID-19 vaccine has been authorized by the U.S. Food and Drug Administration as it demonstrated 95% effectiveness against the SARS-CoV-2 virus. Although the initial vaccine trials showed a favorable side effect profile, there have been concerns regarding activation of aberrant immune responses, triggering autoimmunity. This is a case report of a 68-year-old woman without history of autoimmune conditions, who presented to our emergency department 7 days after receiving the Pfizer-BioNTech COVID-19 vaccine. Her initial symptoms were suggestive of polymyalgia rheumatica, and she had nearly complete response to steroids. Interestingly, she later met criteria for classified systemic lupus erythematous given the development of inflammatory arthritis, positive ANA, and positive dsDNA. The temporal relationship of her symptoms that started 2 days after vaccine administration could suggest a possible association between the Pfizer-BioNTech COVID-19 and the development of systemic lupus erythematous.