Non-alcoholic fatty liver disease is a chronic disease caused by the accumulation of fat in the liver related to overweight and obesity, insulin resistance, hyperglycemia, and high levels of triglycerides and leads to an increased cardiovascular risk. It is considered a global pandemic, coinciding with the pandemic in 2020 caused by the “coronavirus disease 2019” (COVID-19). Due to COVID-19, the population was placed under lockdown. The aim of our study was to evaluate how these unhealthy lifestyle modifications influenced the appearance of metabolic alterations and the increase in non-alcoholic fatty liver disease. A prospective study was carried out on 6236 workers in a Spanish population between March 2019 and March 2021. Differences in the mean values of anthropometric and clinical parameters before and after lockdown were revealed. There was a statistically significant worsening in non-alcoholic fatty liver disease (NAFLD) and in the insulin resistance scales, with increased body weight, BMI, cholesterol levels with higher LDL levels, and glucose and a reduction in HDL levels. Lockdown caused a worsening of cardiovascular risk factors due to an increase in liver fat estimation scales and an increased risk of presenting with NAFLD and changes in insulin resistance.