The major discovery of the novel therapeutic Janus kinase (JAK) inhibitors has been implicated in several dermatological diseases. Recently, studies have shown the efficacy and encouraging results of oral JAK inhibitors as a treatment for alopecia areata (AA). Due to the novelty of this treatment, potential side effects are not fully explored. In this paper, we present a case of a 28-year-old male with a 10-year history of alopecia totalis (AT) treated successfully with tofacitinib with encouraging effects on hair regrowth; however, a significant worsening of the patient’s facial acne was observed four months after AT treatment initiation. JAK inhibitors have promising results in the management of different dermatological conditions including moderate-severe forms of AA with few reported adverse events. Acne exacerbation is a unique observed adverse effect of this therapy. More thorough larger sized studies are needed to further characterize the association between acne exacerbation and the use of JAK inhibitors.