Introduction: We investigated the association between social distress or toxicity and patients’ clinical conditions, demographic characteristics, and social support and networks, and whether this association differs along the distribution of patients’ distress levels. This study included 156 patients treated at King Abdulaziz Medical City, Riyadh, Saudi Arabia.Methods: We used the previously validated Social Toxicity Assessment Tool in Cancer (STAT-C) to assess cancer patients’ distress. We analyzed distress level, the outcome variable of interest, and covariates to show distribution and identify associations. We then used logistic quantile regression for bounded outcomes to assess the association between social distress or toxicity and patients’ clinical conditions, demographic characteristics, and social support and network. As an extension, we examined the interaction between disease status and social support, focusing on the moderating role of social support in attenuating the impact of disease status on social distress.Results: The median age of the patients was 51.2 (SD = 21.4, range 22 to 89), with 48.1% being older than 50 years. Of the 156 cancer patients analyzed, 82 (52.6%) were classified as burdened, and 50% of those with uncontrolled disease status were socially distressed. However, there were more socially distressed patients diagnosed within a year and patients undergoing treatment. There was a greater number of patients who shared their diagnosis with family, colleagues, and neighbors with social distress. The odds of suffering from social distress were higher in younger patients (50 years or younger) than in older patients. Social distress was lower in patients who underwent combined chemotherapy, surgery, and radiation compared with patients who received a single treatment regimen (OR = 0.65, CI, −0.820 to −0.036,p= 0.033). The odds of social distress were 67% higher in patients diagnosed within one year than in patients diagnosed more than one year prior (OR = 1.664, CI, 0.100–0.918,p= 0.015). Patients with uncontrolled disease conditions who shared their diagnosis and treatment with social networks were 48% less likely to experience social distress. Thus, sharing cancer diagnoses with social networks has a statistically significant moderating effect by attenuating the impact of disease status on social distress.Conclusion: Understanding the risk factors for social distress may be important for cancer management. Additionally, identifying the moderating role that patients’ sharing of cancer diagnoses in social networks plays in attenuating the impact of disease status on social distress may provide healthcare providers with valuable insights for holistic culture-specific care.