This paper aims to identify, evaluate, and analyze determinants of the profitability of food enterprises from the Republic of Serbia. The paper determines the nature of the relationship between defined determinants and profitability by applying a panel regression model on a sample of 189 small, medium, and large food enterprises from Serbia in the period from 2011 to 2021. The analysis results showed that the profitability of food enterprises is positively influenced by liquidity and sales growth rate. On the other hand, the indebtedness, size, and materiality of assets have a negative impact on the profitability of food enterprises. Of all analyzed variables, only liquidity does not affect profitability at a statistically significant level. The results of the analysis should be added to the fact that smaller food enterprises, with a lower degree of indebtedness and a smaller share of fixed in total assets, achieve a higher degree of profitability.