This clinical case-control study aimed at investigating the association, if any, of the promoter pentanucleotide microsatellite −2.5 kb (CCTTT)n and the Ser608Leu polymorphisms in NOS2 gene and the −786T>C polymorphism in NOS3 promoter with different IEI, such as MCS, suspected MCS (SMCS), FM, and CFS. Here, NOS2 is linked to myalgic encephalomeyelitis/chronic fatigue syndrome.