Inflammation plays a major role in the etiology of chronic heart failure and in inducing the progression to end-stage heart failure. This chronic inflammation, which accompanies heart failure, is not only local but also systemic and is usually in a state of low-grade but constant activation. Because there is an interrelation between systemic inflammation and neurohormonal activation, almost all anti-remodeling classes of medication have been evaluated for a potential and hidden anti-inflammatory effect. This study aimed to evaluate the effect of sodium-glucose co-trans-porter 2 inhibitors (SGLT2i) (Dapagliflozin or Empagliflozin) on inflammation measured by C-reactive protein levels, erythrocyte sedimentation rate (ESR) and fibrinogen in patients with chronic heart failure when administered together with other standard heart failure medications. We retrospectively enrolled 220 patients with chronic heart failure admitted to our hospital from January 2021 until March 2023. The study included two visits, T0 (the initial visit) and T1 (after six months), to assess if SGLT2i initiation after the first visit (T0) had an effect on the levels of inflammatory biomarkers. SGLT2i showed a reduction in fibrinogen levels, an effect that was present both in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) phenotypes. This was opposite to the dynamics of inflammatory markers in patients who did not receive SGLT2i, where the fibrinogen levels increased in HFrEF and HFpEF subgroups. SGLT2i proved an anti-inflammatory effect, showing a statistically significant reduction in fibrinogen levels in chronic heart failure, irrespective of the phenotype.