The morphology of the hippocampus and amygdala can be significantly affected by a long-term hypoxia-induced inflammatory response. Cardiorespiratory fitness (CRF) has a significant effect on the neuroplasticity of the hippocampus and amygdala by countering inflammation. However, the role of CRF is still largely unclear at high altitudes. Here, we investigated brain limbic volumes in participants who had experienced long-term hypoxia exposure in Tibet (3680 m), utilizing high-resolution structural images to allow the segmentation of the hippocampus and amygdala into their constituent substructures. We recruited a total of 48 participants (48 males; aged = 20.92 ± 1.03 years) to undergo a structural 3T MRI, and the levels of maximal oxygen uptake (VO_2max) were measured using a cardiorespiratory function test. Inflammatory biomarkers were also collected. The participants were divided into two groups according to the levels of median VO_2max, and the analysis showed that the morphological indexes of subfields of the hippocampus and amygdala of the lower CRF group were decreased when compared with the higher CRF group. Furthermore, the multiple linear regression analysis showed that there was a higher association with inflammatory factors in the lower CRF group than that in the higher CRF group. This study suggested a significant association of CRF with hippocampus and amygdala volume, which may be related to hypoxic stress in high-altitude environments. A better CRF reduced physiological stress and a decrease in the inflammatory response was observed, which may be related to the increased oxygen transport capacity of the body.