It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis.