Cachexia, often seen in chronic heart failure (CHF), worsens patient outcomes and survival. Early detection is crucial, and circulating miRNAs offer potential as biomarkers linking heart function, inflammation, and cachexia. This study aimed to identify plasma miRNAs associated with cachexia in CHF and assess their diagnostic and prognostic value. Plasma samples from 150 newly diagnosed CHF patients were analyzed using next-generation sequencing (NGS) and validated by qRT-PCR. A signature of elevated miRNA-628 and reduced miRNA-6803 (↑miRNA-628+↓miRNA-6803) was associated with poor nutritional status, abnormal lab results, and higher cachexia risk. Combining this signature with inflammatory markers perfectly distinguished cachectic from non-cachectic patients (AUC=1.0). This profile increased cachexia risk 19-fold and was linked to significantly shorter survival (median 14 vs. 41 months). Thus, the identified miRNA signature offers strong predictive and diagnostic potential and could complement clinical assessments of CHF patients' nutritional status.