Systemic lupus erythematosus is a multisystem autoimmune disease with varied manifestations involving pulmonary features of pleuritis and pericarditis. These complications may be difficult to diagnose in early stages, as they mimic infectious symptoms. The paper sheds light on diagnostic and treatment challenges associated with lupus pleuropericardial effusions. Glucocorticosteroids (GCs) are usually the first-line treatment, but some patients do not respond to this therapy and require escalation to immunosuppressants or biologics. This is review based on studies published in peer- reviewed journals within past 20 years. The case of a patient with pleural effusion included in the article, in whom the diagnosis of SLE was made through the diagnosis of infection, as well as the cases from the available literature presented in the discussion, well illustrate the problem of symptoms that are part of the picture of SLE, but are non-specific and require differential diagnosis. Early diagnosis and treatment with immunosuppressive, immunemodulating drugs and biologics may lead to better outcomes; further research is needed to explore therapeutic options in difficult cases.