Diffusely abnormal white matter (DAWM) is a non-focal area of mildly increased signal on proton density and T2-weighted images. Advanced imaging techniques (T1 and T2 relaxation and diffusion basis spectrum imaging) compared measures of myelin, axons, oedema and inflammation between males and females with multiple sclerosis in normal appearing white matter (NAWM) and areas of DAWM. In NAWM, males had higher axial diffusivity indicative of axonal damage. In DAWM, MRI measures suggested demyelination in females whereas axonal damage was suggested in males. Both sexes show increased T1, GMT2 and water content in DAWM likely related to oedema.