Lactic acidosis is a frequent laboratory finding in patients with severe exacerbations of asthma. The pathogenesis of lactic acidosis in asthma is not well understood, but it has been presumed, by some, to be generated by fatiguing respiratory muscles. We herein report the cases of three patients with status asthmaticus and lactic acidosis despite pharmacologic muscle relaxation. No common etiologies were found for lactic acidosis that abated after bronchospasm improved and the intensity of pharmacologic therapies was reduced. We review the literature describing lactic acidosis with asthma and discuss mechanisms by which lactic acidosis may occur in patients with status asthmaticus.