After the coronavirus pandemic, hybrid work has become firmly established in many companies. This study investigated the relation of hybrid work and relevant working conditions with the psychological detachment of employees. A written online survey was conducted among 250 employees of a company in the mechanical engineering industry in Germany who worked from home at least part of the time. Multiple hierarchical regression was used for the analysis. The results show that, as expected, the quality of manager-employee communication has a positive (β = 0.13, p < 0.05) and extended work availability a negative effect (β = −0.35, p < 0.001) on psychological detachment. Contrary to the assumptions, however, the proportion of work from home has a positive effect on detachment (β = 0.15, p < 0.05). Regarding the demographic variables, female employees are better able to detach from work (β = −0.36, p < 0.01). The quantitative demands initially show a significant effect, but this disappears as soon as the extended work availability and the proportion of work from home are included in the analysis. The included predictors explain 19% (p < 0.001) of the total variance.Practical Relevance Hybrid work offers the opportunity to organize work more flexibly and thus to adapt it more closely to the needs of employees. The results of this study show that work from home can foster psychological detachment from work, provided that health-promoting working conditions are in place.