The Covid-19 pandemic has increased the vulnerability of cancer patients to psychological symptoms, in addition to treatment modality issues. The present study has aimed to determine the psychological state of Arab cancer patients during the COVID-19 pandemic and to explore the contributing factors. A cross-sectional, descriptive, correlational design with the Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Functional Assessment of Cancer Therapy–Fatigue subscale (FACT-F), and the Functional Assessment of Cancer Therapy–General (FACT-G) were used to collect the data. Out of 291 participants, 60.5% were female; 22.7% were 51–60 years; 31.6% were diagnosed with breast cancer; 44.3% with stage 2 cancer; 23% had contracted COVID-19; and 43.3% had received their first dose of the vaccine. The main study findings are: 74.9% had anxiety, 64.3% experienced depression, 68% suffered from insomnia, and 69.8% had fatigue. Quality of life (QoL) was low among cancer patients who had marked anxiety, depression, insomnia, or fatigue, and these findings were statistically significant (p < 0.05). Predictive factors showed males were 5.09 times more likely to report depression; gynecological cancer patients were 40.4 times more likely to experience insomnia, and patients who had COVID-19 were 5.13 times more likely to report fatigue. The study findings reveal that the COVID-19 pandemic affected the psychological state of cancer patients and had a significant effect on their quality of life. Hence, there is a need to develop a holistic cancer health care approach, which is often limited in Arab countries, to help patients manage these symptoms effectively and to decrease the prevalence of mental health morbidity.