Ensuring appropriate animal welfare is a high priority for the beef industry, and poorly defined abnormalities in the mobility of cattle at abattoirs have gained considerable attention recently. During the summer of 2013, abattoirs throughout the United States reported concerns about nonambulatory or slow and difficult to move cattle and cattle that sloughed hoof walls. This report describes various cattle that developed these mobility problems soon after arrival at an abattoir. Affected cattle had various clinical signs including tachypnea with an abdominal component to breathing, lameness, and reluctance to move. Some cattle sloughed 1 or more hoof walls while in lairage pens and were euthanized. Other cattle recovered after being rested overnight. Affected cattle had serum lactate concentration and creatine kinase activity increased from reference ranges. Histologic findings included diffuse necrosis of the epidermal laminae with degenerate collagen and perivascular infiltration of neutrophils in the underlying deep dermis, and were similar for digits that had and had not sloughed the hoof wall. With the exception of the sloughed hoof walls, the clinical signs and serum biochemical abnormalities observed in affected cattle were similar to those observed in pigs with fatigued pig syndrome, and we propose that fatigued cattle syndrome be used to describe such cattle. Although anecdotal evidence generated concern that cattle fed the β-adrenergic receptor agonist zilpaterol hydrochloride were at greater risk of developing mobility problems, compared with cattle not fed zilpaterol, this condition is likely multifactorial. Strategies to prevent this condition are needed to protect the welfare of cattle.