Background: Systemic lupus erythematosus (SLE) is characterised by the formation of immune complexes in numerous organs, which can result in the loss of immunological tolerance and a range of clinical symptoms. Due to the clinical heterogeneity of the condition and multitude pathways that can result in its expression, making it necessary to identify potential genetic and secretory indicators of SLE to aid early diagnosis in asymptomatic or susceptible patients. Here, the demographics, the clinical manifestations, cytokines interferon α (IFN-α) and Toll-like receptor 7 (TLR-7) as well as expression levels of human integrin alpha M chain (ITGAM) and tumour necrosis factor (TNF) alpha induced protein 3 (TNFAIP3) genes were investigated in SLE patients in comparison with healthy subjects. Patients and Methods: Sixty patients clinically diagnosed with SLE, along with 60 age-matched healthy individuals (control) were recruited in the study. Serum levels of cytokines (IFN-α and TLR-7) as well as expression levels of ITGAM and TNFAIP3 genes were measured using enzyme-linked immunosorbent assay (ELISA) techniques and real-time qualitative polymerase chain reaction (RT qPCR) respectively. Results: The results obtained showed significant overexpression of IFN-α in SLE patients compared to healthy subjects (i.e. 344.79±30.72 U/mL, SLE vs. 234.88±28.55 U/mL, healthy subjects) (p = 0.01). Similarly, the SLE patients had significantly higher mean TLR-7 levels compared to healthy subjects (i.e. 86.48±57.41 U/mL, SLE vs. 426.66±23.20 U/mL, healthy subjects) (p = 0.001). The gene expression analysis showed upregulation of ITGAM and TNFAIP3 in SLE patients by 15.48 folds and 43.08 folds respectively. Also, receiver operating characteristic analysis showed that ITGAM had specificity of 100% with the sensitivity of 98% (AUC = 1.00), while TNFAIP3 had the specificity of 98% with the sensitivity of 93% (AUC = 0.97). Conclusion: Cytokines IFN-α and TLR-7 as well as genes ITGAM and TNFAIP3 proved as diagnostic markers of SLE as well as putative role in disease management.