Background: Epilepsy and seizures occurrence are closely interwoven with brain inflammation. The inflammatory response is largely mediated by microglia, which are under strong circadian regulation. Circadian rhythms are 24-hour variations in physiological function orchestrated by a network of autoregulatory genes, including its key component, Bmal1. Here we explored the impact of Bmal1 knock down in microglial cells on seizure susceptibility and the CNS-immune profile.Methods: Forty young adult Bmal1-Cx3CR1Cre-ER mice were injected with either tamoxifen (40 mg/kg; IP; daily for 10 days) to induce microglial-specific Bmal1 knock-down (Bmal1-KD) or vehicle (controls). A subset of this cohort was implanted with electrodes for electroencephalographic (EEG) recordings and underwent an injection of a low dose of kainic acid (KA; IP; 15 mg/kg) to test seizure susceptibility. Naïve and KA hippocampi were extracted and analysed by qPCR and semi-quantitative cytokine array immunoblotting.Results: Microglial Bmal1-KDs were more susceptibility to develop seizures (136.7s ± 27.49s) in comparison to controls (onset 592.7s ± 139.7s; P<0.0001) and displayed a significantly increased seizure severity measured by total EEG power (P<0.0002). Pro-inflammatory cytokine HMGB1 was significantly upregulated at baseline in Bmal1-KDs, while HMGB1 (P<0.05), iNOS, TNF-α and TNFRII (P<0.01) were significantly upregulated in Bmal1-KDs compared with controls as early as 30 minutes after KA administration. Interestingly, G-CSF was significantly upregulated and IL-1α downregulated at the protein level post-KA in Bmal1-KDs compared to controls. Conclusions: Microglial-specific depletion of Bmal1 led to a disrupted electrophysiological and immune phenotype in otherwise healthy mice. Future studies will examine how these mice develop epilepsy.