Hydroxychloroquine is effective for treating a number of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine is generally safe and may be prescribed to pregnant women. Although current guidelines recommend initiating hydroxychloroquine when considering pregnancy, the drug can cause adverse effects such as acute generalized exanthematous pustulosis, which should be carefully evaluated. A 30-year-old pregnant woman with systemic lupus erythematosus at 16+5 gestational weeks was referred to our tertiary centre for persistent proteinuria and alopecia. Tacrolimus was initiated and the dose of prednisone was increased. At 20+3 weeks of gestation, hydroxychloroquine was administered to allow for a dose reduction of prednisolone. Proteinuria gradually improved as the pregnancy course stabilized. At 27+1 weeks of gestation, generalized pustular exanthema developed, presumably due to hydroxychloroquine. After analysis of the clinical course and skin lesions, she was considered to have either acute generalized exanthematous pustulosis or generalized pustular psoriasis. Despite discontinuing hydroxychloroquine, the skin lesions worsened dramatically, and infliximab therapy was required. After one course of infliximab treatment, exanthema gradually subsided. The final diagnosis was acute generalized exanthematous pustulosis, based on the clinical course and pathological findings. At 30 weeks, the pyothorax developed because of the pyogenic skin lesion and the compromised immune system, and long-term antibiotic therapy was required until 32+4 weeks, after which, she underwent caesarean section. Although introducing hydroxychloroquine is occasionally necessary during pregnancy, it is preferable to initiate hydroxychloroquine in the preconception period and not after pregnancy because of the possible adverse effect which can alter perinatal prognosis. Rheumatologists should consider the potential risks of hydroxychloroquine.