OBJECTIVE We studied the hypothesized effects of changes in self-rated health (SRH) on subsequently assessed changes in the levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglycerides (TRI), separately for men and women. We also investigated the reverse causation hypothesis, expecting the initial changes in the levels of serum lipids to predict subsequently assessed changes in SRH levels. METHODS We used a longitudinal design and controlled for possible confounders known to be precursors of both SRH and the above three serum lipids. Participants were apparently healthy men (N = 846) and women (N = 378) who underwent a routine health check at three points of time (T1, T2, and T3); T1 and T3 were on the average 40 and 44 months apart for the men and women, respectively. CONCLUSIONS For the men, relative to T1 SRH, an increase in T2 SRH was associated with an increase in the T3 HDL-C levels relative to T2 HDL-C and with a decrease in the T3 TRI levels relative to T2 TRI. For the women, initial changes in the SRH levels did not predict follow-up changes in either of the lipids. For both genders, the reverse causation hypothesis, expecting the T1-T2 change in each of the serum lipids to predict T2-T3 change in SRH, was not supported. For the men, there is support for the hypothesis that the effects of SRH on morbidity and mortality, found by past meta-analytic studies, could be mediated by serum lipids.