Background: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis. Objective: Using 11 C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing–remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity. Methods: Mean 11 C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T 2 * (q-T 2 *) abnormalities, and normal-appearing cortex. The relative difference in cortical 11 C-PBR28 uptake between patients and 14 controls was used to classify cortical lesions as either active or inactive. Disease burden was investigated according to cortical lesion inflammatory profiles. The relation between q-T 2 * and 11 C-PBR28 uptake along the cortex was assessed. Results: 11 C-PBR28 uptake was abnormally high in cortical lesions in RRMS and SPMS; in SPMS, tracer uptake was significantly increased also in normal-appearing cortex. 11 C-PBR28 uptake and q-T 2 * correlated positively in many cortical areas, negatively in some regions. Patients with high cortical lesion inflammation had worse clinical outcome and higher intracortical lesion burden than patients with low inflammation. Conclusion: 11 C-PBR28 and 7T imaging reveal distinct profiles of cortical inflammation in MS, which are related to disease burden.