Food intake is timed to primarily occur within the active phase of the day; whether that be during the light for diurnal or the night for nocturnal animals. The suprachiasmatic nucleus of the hypothalamus, the “master clock” within the brain, is essential for timing of the animal’s physiology to be aligned with the external light/dark cycle. Forced disruption to activities so that they no longer lie in the light/dark cycle, such as shift work and jet lag, predisposes the individual to metabolic disease and its complications. Zinc finger homeobox 3 (Zfhx3) is a transcription factor that is essential for the development of the mouse brain, but it is also expressed in discrete regions in the adult mouse brain including the suprachiasmatic nucleus. Zfhx3 expression is crucial for time-keeping in absence of a light/dark cycle: global and conditional knock-out of Zfhx3 renders the mice arrhythmic in the absence of external cues. In addition to a role in circadian timekeeping, Zfhx3 is also highly expressed in brain regions that are important for the regulation of energy balance – such as the arcuate hypothalamic nucleus and the nucleus of the solitary tract – though its role in these areas is not known. We hypothesised that global conditional knockdown of Zfhx3, in addition to its impact on arrhythmia in free-running conditions, would also alter feeding behaviour and energy homeostasis due to its expression in hypothalamic and hindbrain regions. To investigate this, we examined the metabolic phenotype of tamoxifen-induced knock-down of Zfhx3 inZfhx3Flox/Flox;UBC-Cre+ mice compared to littermate controls using indirect calorimetry (males: n = 3-5, females: n = 4-6). Interestingly, we found that the knock-down mice gained significantly more weight in the 4-6 weeks post-tamoxifen treatment than their wild-type littermates (Males: +4.41g ± 0.19 SEM, p = 0.04, females: +3.05g ±0.44 SEM, p = 0.05). Echo-MRI indicated that this was due to increases in both fat and lean mass. Weight gain was most pronounced in the male Zfhx3-knockdown mice, which could be attributed in part to their slightly higher food consumption (+1.49g ± 1.48 SEM, Genotype*Time: p = 0.018) during the indirect calorimetric experiment, which was not observed in female mice. Not only did the male Zfhx3-knockdown mice eat more food, they also expressed an abnormal rhythm of food intake in the light/dark cycle. This was accompanied by reduced amplitude and advanced phase in both activity (Amplitude: -10.59 AUC ±1.76, p = 0.036; Phase: +2.52 hours ±0.45 SEM, p = 0.018) and energy exchange (Amplitude: -7.3 AUC ±0.87 SEM, p = 0.036; Phase: +2.5 hours ±0.38 SEM, p = 0.036); neither of which were observed in the female knockdown mice. We can conclude that Zfhx3 is involved in regulating energy homeostasis given the increased weight gain in both male and female knockdown animals. These results also suggest that, not only is expression of Zfhx3 in adult mice important for maintaining physiological circadian rhythmicity even when external cues are present, but there is also a sexually dimorphic effect.