Considerable scientific evidence has been published on the effectiveness of massage in different conditions, but it remains unclear whether this effectiveness is modulated by the profile of patients. The aim of this study was to compare the effects of a 21-min myofascial therapy protocol on stress responders and nonresponders stressed in the laboratory with a cold pressor test. Dependent variables included heart rate variability (HRV), blood pressure, and salivary markers such as flow rate, cortisol, immunoglobulin A (IgA), and -amylase activity. A controlled, repeated measures, single-blind trial was conducted in 30 Caucasian students with a mean (SD) age of 20.70 (4.50) years. We found no significant between-group differences in descriptive characteristics or in any preintervention outcome measure. Analysis of covariance revealed significant increases in HRV index (F = 0.18, p = .01), salivary flow rate (F = 0.16, p = .02), and salivary IgA concentration (F = 4.36, p = .04) and significant decreases in the low-frequency domain (F = 0.18, p = .04) and LF-high-frequency ratio (F = 0.18, p = .01) in the stress responder group in comparison to the nonresponder group. In conclusion, a better response to massage was observed in stress responders than in nonresponders across various HRV parameters and salivary measures.