Metabolic abnormalities and peripheral inflammation have been increasingly reported in patients at their first episode of psychosis (FEP) and associated with increased mortality. However, the impact of an abnormal metabolic-inflammatory status on the psychiatric outcome of FEP is understudied. This study aimed 1) to combine metabolic and inflammatory variables in factors accounting for an overall metabolic-inflammatory status in FEP patients; 2) to explore the association between these factors and clinical outcome at 1 year. We recruited 43 FEP patients and 50 healthy controls (HC). At baseline (T1) we measured high sensitivity C-reactive protein (hsCRP) as inflammatory biomarker, and body mass index (BMI), lipid profile and gluco-metabolic parameters (glycated haemoglobin (HbA1c) and fasting glucose) as metabolic variables. Using a principal component analysis (PCA) we gathered all variables in factors accounting for both inflammation and metabolic status. In patients, we assessed symptoms severity at T1 and after 1-year (T2) as well as T2 treatment response. FEP showed higher HbA1c (p = 0.034), triglycerides (TG) (p = 0.044) and BMI (p = 0.023) than HC. PCA identified 3 factors. Factor 1, accounting for hsCRP, TG and BMI, was associated with T1 negative symptoms severity (p = 0.018) and predicted T2 positive symptoms severity (p = 0.003), overall symptoms severity (p = 0.004), general psychopathology (p = 0.001) and treatment response (p = 0.007). A combined inflammatory-metabolic factor proved to predict the clinical course of psychosis and offer an important target for early interventions.