While type I IFN signatures have been extensively characterized, the systemic relevance of circulating type III IFNs and the clinical implications of the relative balance between IFN types I, II, and III remain insufficiently explored.<h4>Methods</h4>In this real-life, exploratory study, plasma concentrations of IFN-α2, IFN-β, IFN-γ, IFN-λ1, and IFN-λ2 were measured in patients with SjD (n = 59), SLE (n = 35), and healthy controls (n = 30). Here, IFNL1 is linked to systemic lupus erythematosus.