Systemic lupus erythematosus (SLE) is a complicated chronic autoimmune disorder. Several genetic and environmental factors were suggested to be implicated in its pathogenesis. The main objective of this study was to examine how exposure to selected environmental factors was associated with SLE risk to support the development of disease preventive strategies. A case–control study was conducted at the Rheumatology outpatient clinic of Alexandria Main University Hospital, in Alexandria, Egypt. The study sample consisted of 29 female SLE patients, and 27 healthy female controls, who matched the cases on age and parity. Data were collected by a structured interviewing questionnaire. Blood levels of lead, cadmium, and zinc of all participants were assessed by flame atomic absorption spectrometry. The multivariate stepwise logistic regression model revealed that five factors showed significant association with SLE, namely living near agricultural areas, passive smoking, blood lead levels ≥ 0.075 mg/L, and exposure to sunlight (odds ratio (OR) 58.556, 95% confidence interval (CI) 1.897–1807.759, OR 24.116, 95% CI 1.763–329.799, OR 18.981, 95% CI 1.228–293.364, OR 9.549, 95% CI 1.299–70.224, respectively). Whereas walking or doing exercise were significantly protective factors (P = 0.006). The findings of this study add to the evidence that SLE can be environmentally induced. Preventive measures should be taken to address the environmental risk factors of SLE.