Chiari malformation type I (CMI) provides an opportunity for examining possible moderators of allostatic load. CMI patients who had (n = 43) and had not (n = 19) undergone decompression surgery completed questionnaires regarding pain, disability, and loneliness, and provided serum samples for IL-6, CRP, estrogen, and free estradiol assays, and saliva samples to assess diurnal cortisol curves. ANOVAs examining surgical status (decompressed versus non-decompressed), loneliness (high vs. low), and disability (high vs. low) as independent variables and biomarker variables as dependent factors found that loneliness was associated with higher levels of cortisol, F(1, 37) = 4.91, p = .04, η²_P = .11, and lower levels of estrogen, F(1, 36) = 7.29, p = .01, η²_P = .17, but only in decompressed patients. Results highlight the possible impact of loneliness on biological stress responses and the need to intervene to reduce loneliness in patients with symptomatic CMI.