Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, which, in the cases of high activity, results in extensive damage to various tissues and organs, as well as promotes early patient disability. Most drugs used for the treatment of SLE are currently prescribed off-label, since this specific indication is not reflected in their prescribing information. At the same time, the advent of belimumab (Benlysta®), an innovative biological product for the treatment of SLE, which represents the most severe connective tissue disorder, provided patients with an access to a highly effective targeted therapy, which specifically impacts one of the main mechanisms of the disease. The innovative and proprietary product, Belimumab, has a relatively high cost, which, as the healthcare budget is restricted, requires that a pharmacoeconomic evaluation be completed of combined use of belimumab with standard of care (SoC) versus SoC alone. The present study showed that the use of belimumab combined with SoC in patients with SLE was, clearly, associated with additional costs compared to SoC alone. However, given low incidence of the condition, the overall increase in costs is unlikely to be significant. On the other hand, it was noted that the high belimumab efficacy resulted in lower direct costs of treating the SLE (cardiovascular, cutaneous, and pulmonary) complications, as well as the costs of hospital care. A comparative analysis has demonstrated that the annual cost of treatment with belimumab was similar to the cost of other genetically engineered biological products, which have already been included into the List of Vital and Essential Drugs used for rheumatic diseases, particularly rheumatoid arthritis. In this view, the use of belimumab, which represents the only targeted drug for SLE, could be considered during the review of policy for subsidised drug provision to patients with this condition.