Background: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease characterized by short, repeated, and self-limiting attacks of fever and serositis. Subclinical inflammation can persist in the periods with no symptoms and result in amyloidosis even with colchicine treatment. Neopterin and calprotectin have been considered essential players in inflammation and immune response. Aim: The study was aimed to measure serum levels of neopterin and calprotectin in patients with FMF in the attack-free period. Methods: A total of 160 participants were recruited from the rheumatology department in this single-center, case–control study. Individuals having the inclusion criteria were divided into healthy controls (n = 80) and FMF (n = 80). The laboratory data were acquired from the electronic registration database. Serum calprotectin and neopterin were measured with ELISA test kits. FMF patients and healthy controls’ laboratory findings were compared. Results: FMF patients’ serum red cell distribution width (RDW), calprotectin, and neopterin values were significantly higher compared to healthy controls. There were no statistically significant differences between calprotectin and neopterin regarding gender, family history, and colchicine response of the FMF patients. Conclusions: Calprotectin, neopterin, and RDW can be valuable marker candidates to be used in the follow-up of subclinical inflammation in FMF patients.