The occurrence and spatial distribution of intestinal helminth infection in children is fairly well understood. However, knowledge on how helminth infections govern intestinal morbidity is scarce. We conducted a cross-sectional study to assess and quantify the relationship between single and multiple species helminth infection with clinical and self-reported morbidity indicators and nutritional status in Champasack province, southern Lao People's Democratic Republic (Lao PDR). A random sample of 1313 children, aged 6 months to 12 years, from villages in nine rural districts were enrolled and examined for helminth infection using duplicate Kato-Katz thick smears. Morbidity was assessed by self-reported symptoms, coupled with clinical examination and appraisal of nutritional status and anaemia. Bivariate and multivariate logistic regression was employed to study associations between helminth infection and morbidity indicators and anaemia. We found considerable morbidity among the surveyed children, including hepatomegaly (13.7%), pale conjunctiva (13.2%) and abdominal pain (10.4%). Anaemia was recorded in 60.4% of the children, whilst signs of stunting and low body mass index (BMI) were observed in 49.8% and 33.3% of the surveyed children, respectively. Hookworm and Opisthorchis viverrini were the predominant helminth species with prevalences of 51.0% and 43.3%, respectively. The prevalence of Schistosoma mekongi in the surveyed children was 5.6%. Multiple species helminth infections were recorded in 40.4% of the study cohort. Morbidity was associated with specific helminth species infection (e.g. S. mekongi with hepatomegaly; adjusted odds ratio (aOR): 9.49, 95% confidence interval (CI): 2.07–43.51) and multiparasitism (e.g. two or more helminth species with abdominal pain; aOR: 2.40, 95% CI: 1.46–3.93). Anaemia was associated with hookworm infection (aOR: 1.64, 95% CI: 1.16–2.34) and multiparasitism (aOR: 1.64, 95% CI: 1.18–2.29). Low BMI was associated with O. viverrini infection (aOR: 1.68, 95% CI: 1.14–2.49) and multiparasitism (aOR: 1.42, 95% CI: 1.01–2.00). The multiple strong associations reported here between helminth infections (single or multiple species) and intestinal morbidity among children in rural parts of southern Lao PDR call for concerted efforts to control helminth infections, which in turn might improve children's health and development.