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This study aimed to investigate the effect of different preferences of food-derived odors (common food flavors/spices) on the appetite, immune system, and CNS of mice through 15 days of olfactory exposure. According to the ranking of sniffing duration, beef essence was chosen as a pleasant odor, while garlic essence was chosen as an unpleasant odor. Results showed that food intake and body weight gradually increased in all groups, with the lowest values observed in the garlic odor group. Unpleasant garlic odor suppressed the mRNA transcription levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) in the hypothalamic arcuate nucleus, along with elevated leptin levels, thereby inhibiting food intake and causing body weight loss. In addition, the serum TNF-α, IL-2, and IL-6 levels in the garlic odor group were significantly higher than those in the beef and control groups, which indicated that the immune system may be impaired by the exposure to unpleasant garlic odor. Furthermore, pleasant beef odors could promote the differentiation of hippocampal neurons and the levels of brain-derived neurotrophic factors and glial cell line-derived neurotrophic factor, which may have great potential in improving neurological disorders. Conclusively, unpleasant odors may suppress immune function or modulate the CNS by establishing an odor-CNS-immune pathway, while pleasant food odors affect only the CNS. The present study preliminarily provides novel insights that different preferences for food odors could affect the body weight, immune system, and CNS. It may serve as a reference for further research and development of aromatherapy as an adjuvant medicine and therapeutic method.