Unemployment is a factor that heavily influences the output of each economy. It is, therefore, one of the main concerns of any government worldwide. This study identifies key determinants of unemployment. By constructing an econometric model for the registered unemployment rate in Slovakia, the period from 2013 to 2022 was under scrutiny, while the impact of the COVID crisis was considered in the model through a dummy variable. Potential determinants of unemployment were selected based on theoretical knowledge and other scientific works, that is, average interest rates, gross minimum wage, GDP, inflation, exports, imports, government spending, corruption index, COVID-19 crisis, and month of the year. The final relevant factors for unemployment were tested and validated: interest rates, GDP, inflation, government spending, and exports. These study results may be valuable for the government when designing targeted interventions to optimise the unemployment rate in Slovakia or similar economies by influencing other macroeconomic indicators.