Introduction: Systemic lupus erythematosus (SLE) is a connective tissue disorder which involves immune system dysregulation. Micro-ribonucleic acids (MiRNAs) up and down regulation are implicated in its development. Aim of the work: To examine the expression levels of certain miRNAs (miR-17, miR-20a, miR-106a, and miR-142-3p) in SLE patients and to investigate which miRNAs are involved in the pathogenesis of SLE, in order to be used as diagnostic or prognostic biomarkers. Patients and methods: 60 patients and 60 matched control were included. SLE disease activity index 2000 (SLEDAI-2 K) was assessed. Assessment of serum miRNAs was done using real-time quantitative polymerized chain reaction. Results: The median age of patients was 29.5 years (24–32) and they were 59 females and 1 male with a median disease duration of 24 (20–48) months and SLEDAI of 5.5 (2.3–9). miR-17a, miR-142, miR-20a and miR-106a were significantly lower in patients (22.5 ± 2.2; 22.8 ± 2.2; 23.4 ± 2.4 and 22.6 ± 2.2) compared with control (23.8 ± 2.1; 24.7 ± 2.2; 25.1 ± 2.4 and 24.4 ± 2.3) (p = 0.002, p 22.6, >22.1 and >22.8 respectively; area under the curve was 67, 72, 70 and 76% at p-values p = 0.19, p