Fatal intoxications with opioids are known to be associated with an increased lung weight, as well as with brain and pulmonary edema and urinary retention. However, there is evidence to suggest that fatal intoxications with non-opioid substances are also associated with increased lung weight; however, the latter aspect has not been comprehensively analyzed. To determine to what extent opioid and non-opioid substances are associated with increased lung and brain weight, we studied these organs in cases where the cause of death was attributed to intoxication with a single agent. Using data from cases autopsied at the National Board of Forensic Medicine (NBFM) in Sweden from 2009 through 2019 where the cause of death was attributed to a single substance, we created models of combined lung weight and brain weight. The models used age and sex as predictors as well as nested varying effects for the specific intoxicant and category of intoxicant. Suicidal hanging with negative toxicology cases served as controls. The population majority was male among both intoxications (68%) and controls (83%). The most common single substance group was opioids. All tested substances were associated with heavier lungs than controls, with the largest effect in the opioid group. Our findings show that several substances are associated with increased lung weight and that among intoxication deaths there is no difference in expected brain weight between substances. Hence, heavy lungs, without a reasonable explanation, should prompt a broad toxicological screening.