Smokers report an increase in upper respiratory infections in the early phase of stopping smoking. One possible cause is a depletion in secretory immunoglobulin A (S-IgA) which has been observed in one study. The present study sought to establish this finding in smokers using nicotine patches. Ninety-two smokers, trying to stop smoking, were assessed whilst smoking and for up to six weeks of abstinence. All smokers were prescribed 15 mg 16-h nicotine patches. Among abstinent smokers, changes in S-IgA and saliva volume were assessed. During the preliminary analyses, we observed that for the pre-smoking cessation measure a longer time since the last cigarette was significantly related to lower S-IgA levels (P = 0.006). Consequently, the main analysis, of changes in S-IgA from pre-cessation to post-cessation, was confined to those who had smoked within 0.5-1.5 h of the pre-cessation measure (n = 51). There was a significant decline in S-IgA, relative to pre-smoking abstinence levels, following abstinence of one day (P = 0.027), but levels returned to pre-abstinence values after one week. There was no evidence of any significant changes in saliva volume following smoking cessation, relative to pre-cessation levels. Users of 15 mg patches are likely to experience a decline in S-IgA levels on the first day of smoking cessation, independent of saliva volumes, and this decline in S-IgA is likely to occur acutely, within the first few hours of smoking abstinence. This acute drop in S-IgA appears to stem from a factor other than depletion of nicotine from the body. The observed decrease in S-IgA may help to explain the increased susceptibility of smokers to upper respiratory tract infections in the immediate post-cessation period.