OBJECTIVE: A link between dyspepsia symptoms and weight loss is controversial. We aimed to determine whether or not weight loss is a marker of dyspepsia. METHODS: Independent community-based cross-sectional studies. Subjects were randomly selected from the general population in Sydney, Australia. All subjects completed validated community health surveys. Two distinct data collections were used; the first as a training sample (N = 888) and the second as a validation sample to confirm the findings of the first (N = 2,907). The study was focused on weight loss, which was categorized as (a) any weight loss, (b) substantive weight loss (≥3 kg), and (c) weight loss expressed as percentage of body weight. RESULTS: All dyspepsia symptoms studied were positively associated with weight loss although the strength of association did vary. Nausea and vomiting were most strongly associated with weight loss as were meal-related complaints such as postprandial fullness. Similarly, clusters formed based on symptoms were strongly differentiated in terms of weight loss with clusters characterized by nausea, vomiting, and early satiety/postprandial fullness reporting 25-30% weight loss prevalence over the previous 3 months compared with around 10% prevalence in clusters characterized by low dyspepsia symptom burden. Weight loss ≥3 kg followed a similar pattern but with a prevalence approximately half that of any weight loss, while weight loss expressed as percentage of body weight followed the same pattern. CONCLUSIONS: Dyspepsia symptoms are clearly and, in some cases, strongly associated with weight loss, both any loss of weight and substantive weight loss. Weight loss should be considered a warning symptom of dyspepsia.