Due to COVID-19, many countries, like Spain, imposed lockdown on the entire population to prevent the virus from spreading. The purpose of this exploratory study is to investigate the severity of psychological symptoms, dyadic adjustment, and parental stress of parents during the first three weeks of the outbreak. It also aims to identify several risk factors that contribute to this distress. A total of 727 parents completed a form on an online platform with sociodemographic data, BSI- 18, EAD-13, and the Spanish version of the PPS. Linear regression analyses were used to explore the significant associations between the sample characteristics (sociodemographic variables and their lockdown circumstances) and parents’ psychological symptoms, dyadic adjustment, and parenting stress level during the COVID-19 epidemic. Most parents maintained good emotional, personal, conjugal, and family stability; however, female gender, not living with the partner, having a child with a mental disorder and were unable to balance the work and family lives were significantly associated with greater psychological distress. Being receiving psychiatric or psychological treatment has also been associated with poorer psychological and partner adjustment during the outbreak. It is essential to continue researching the impact of lockdowns on families so that, both the government and public health authorities, can offer resources to the most vulnerable families.