We documented four cases of systemic lupus erythematosus (SLE) presenting with pleuritis as the initial disease manifestation. The diagnosis was challenging because, atypically, all patients were elderly and 3 of the 4 patients were men. Furthermore, SLE pleuritis, characterized by lymphocytic pleural effusion and high ADA activity, is difficult to differentiate from tuberculous pleurisy. A detailed physical examination, blood tests, and urinalysis are therefore indispensable to ensure an accurate diagnosis. We also reviewed the previously published case reports on SLE patients presenting with pleuritis and discussed the relevant findings.