Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, < 0.0001). HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID.