BackgroundSerious mental illness (SMI) is a debilitating medical condition that causes stress and challenges for the family caregivers (FCs) of affected patients, increasing their caregiver burden (CB). This situation can activate attachment styles (AS) and trigger negative emotions, further contributing to CB. Given that AS and cognitive-emotional regulation (CER) can affect the CB of FCs of patients with SMI, the aim of this study was to evaluate the relationship between CB with AS, and CER among the FCs.MethodsThis cross-sectional descriptive-correlational study was carried out in May–November 2022. Participants were 278 FCs of patients with SMI consecutively recruited from Roozbeh leading psychiatric hospital, Tehran, Iran. Data were collected using a patients’ demographic and clinical characteristics questionnaire, an FCs’ demographic characteristics questionnaire, the Attachment Style Questionnaire, the Cognitive Emotion Regulation Questionnaire, and the Burden Scale for Family Caregivers, and were analyzed using the SPSS software (v. 16.0).ResultsCB had significant inverse relationship with secure AS (r = − 0.262) and significant positive relationship with fearful AS (r = 0.194) and dismissive AS (r = 0.242) (P < 0.01). Moreover, CB had significant inverse relationship with adaptive CER strategies and significant positive relationship with maladaptive CER strategies (P < 0.001). Regression analysis also showed that CB had significant relationship with secure AS and catastrophizing, rumination, self-blame, and positive refocusing CER strategies (P < 0.05).ConclusionThis study concludes that AS and CER can impact CB. There is a negative relationship between secure AS and CB, as well as between adaptive CER strategies and CB. Conversely, there is a positive relationship between avoidant AS and increased CB, as well as between maladaptive CER strategies and CB. It is recommended to adopt strategies that promote the use of secure AS and adaptive CER among the FCs of patients with SMI.