The choroid plexus (ChP) is a highly vascularized non-neural tissue located in the brain ventricles and is responsible for the production of a large part of the cerebrospinal fluid (CSF). In addition, the epithelial cells of the ChP synthesize neurotrophic factors and other signalling molecules into CSF and act as a blood-cerebrospinal fluid barrier. Importantly, ChP cells harbour a robust circadian oscillator that may control ChP function and may play an important role in the circuitry between brain clocks. In this study, we aimed to find out whether the ChP clock is sensitive to a robust immune challenge. The sensitivity of the ChP clock to inflammation was first investigated ex vivo by monitoring bioluminescence rhythms in organotypic ChP explants in real time after lipopolysaccharide (LPS) treatment (acute and long-term effect) and co-cultivation with polarized macrophages. These experiments demonstrated the resilience of the ChP clock to the immune challenge. To determine whether a systemic pro-inflammatory state affects the ChP clock in vivo, we injected mice with LPS or saline 3 h after the lights off and collected samples of ChP and liver at 6-h intervals to determine daily profiles. Although the liver clock was affected by inflammation, the ChP clock was resistant to lipopolysaccharide treatment and the immune challenge. The data demonstrate the high resistance of the ChP clock to inflammation and highlight its role in protecting the brain from neuroinflammation.