Patients with paroxysmal nocturnal haemoglobinuria (PNH) are deficient in monocytic CD14. The aim of this research was to determine the interrelationships among periodontal disease status, local levels, and monocytic secretion of inflammatory mediators in patients with PNH and matched controls. This study utilised a cross sectional, non-randomised design. PNH patients and matched controls (age, race, gender) were assessed for periodontal status, levels of PGE2 and IL-1beta within the gingival crevicular fluid (GCF), and levels released from lipopolysaccharide (LPS) stimulated peripheral blood monocytes in culture. Results indicate no statistical differences in extent and severity of periodontal disease or GCF mediator levels between the two groups. Monocyte responses to LPS demonstrated significant differences in PGE2 (P = 0.0009) and IL-1beta (P = 0.003) secretion with PNH monocytes secreting significantly less than controls. A significant positive association was found between the monocytic and GCF levels of PGE2 for all subjects (P = 0.003), PNH (P = 0.015), and control (P = 0.049) groups. This study demonstrated that GPI anchor deficient monocytes have reduced expression of inflammatory mediators in vitro.