Abstract: Introduction: Depression is an extremely widespread disorder that is also highly impactful on the quality of life and general health of individuals, on a global scale. The aim of this study was a preliminary assessment of a potential non-pharmacological treatment, based on extremely low frequency and intensity electromagnetic fields (ELF-EMF), which could potentially reduce the impact of depression on the lives of sufferers. Materials and methods: A preliminary case-control study based in 2centres was conducted during the second half of 2020. The recruited participants were subject either to ELF-EMF treatment (Group α) or to a placebo treatment (Group β) for a total of 5 sessions. Treatment involved non-focused exposure using a radiant mat associated with focused exposure in the cranial area using the same ELF-EMF parameters. Each individual session lasted 36 min and the same ELF-EMF program was used for all 5 therapeutic sessions. The effects of treatment were evaluated by giving the subjects the following self-administration tests: Zung Self-Rating Depression Scale (SDS), Beck Depression Inventory Scale (BDI), and Short-Form 12 (SF12). The tests were administered before starting the treatment cycle (T0), after the 5 sessions (T1), and at a 2 month follow-up (FU). Results: Statistical significance indicating an improvement in the depressed state perceived by the participants was achieved with both the SDS and the BDI, at T1 (T1: SDSα 37.8, SDSβ 46.6, p = 0.012; BDIα 8.7, BDIβ 20.4, p = 0.004) and persisting at FU (T1: SDSα 39.1, SDSβ 49, p = 0.037; BDIα 10, BDIβ 19.9, p = 0.04). As regards SF12, the mental part of the test (MCS12) exhibited a significant improvement at T1in the treated group compared to the placebo (MCS12α 47.40, MCS12β 40.48, p = 0.048), but this was not confirmed at FU. During the treatment period there were no drop-outs from the 2 groups and no adverse events were reported in the treatment group. Conclusions: Treatment with ELF-EMF demonstrated safety and efficacy for reducing the gravity of perceived depressed state.