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Simple Summary: Spain is the fifth largest beef cattle producer in the European Union. Animal tuberculosis (TB) is one of the primary limitations of beef cattle farming in the affected countries. The closed herd policy is an effective tool against animal TB, being based on rearing the calves born on the farm for replacement. When the disease appears on a farm, a series of decisions must be taken that will cause substantial losses for three main reasons: First, the final balance generated by the slaughter of infected animals; second, the lower sales revenue derived from the replacement of the slaughtered cattle; and third, the costs incurred from immobilizing the rest of the animals in the herd. Quantifying the impact of TB is determined by the loss of profit, with the consequences being different in relative terms depending on each farm, where those with larger numbers of head of cattle are more resilient to a given number of positive cases. It also contributes to the debate about the optimal balance of cost sharing between the government and farmers. Pasture-based livestock farming generates income in regions with limited resources and is key to biodiversity conservation. However, costs derived from fighting disease can make the difference between profit and loss, eventually compromising farm survival. Animal TB (TB), a chronic infection of cattle and other domestic and wild hosts, is one of the primary limitations of beef cattle farming in some parts of Europe. When an animal tests positive for TB, a loss of profit is caused in the farm, which is due mainly to the animal's slaughter, replacement of the slaughtered animal and the need to immobilize the rest of the herd. We estimated the economic impact in terms of loss of profit as a result of incremental costs and forgone incomes. We show that farms with a larger number of heads are more capable of dealing with the loss of profit caused by the disease. The quantification of the loss of profit contributes to the ongoing debate on the co-sharing of TB costs between government and farmers. The compensation farmers receive from the public administration to mitigate the economic effects of the disease control interventions is only intended to balance the loss due to slaughter of the infected cattle, being the loss of profit a more global concept. [ABSTRACT FROM AUTHOR]