Salt-Inducible Kinase 3 (SIK3) has emerged as an important regulator of metabolism; however, its role in regulating body weight and energy balance, particularly in the hypothalamus, remains unclear. Here, we show that SIK3 expression is increased in the hypothalamus of obese mice. Inactivation of SIK3 in orexigenic neurons reduces food intake, increases energy expenditure, and promotes white adipose tissue browning, protecting mice from high-fat diet-induced obesity. Consistently, pharmacological inhibition of SIK3 also reduces body weight and adiposity in diet-induced obese mice, primarily by reducing food intake, while improving metabolic health. These effects are associated with enhanced central leptin and insulin signalling, as well as altered activity and localisation of key metabolic transcriptional regulators. Together, our findings identify SIK3 as an important regulator of energy balance and suggest that SIK3 may represent a novel therapeutic target for obesity.